Clinical Application of Peripheral Blood Biomarkers for Solid Tumors

Xinru Tu , Mengyan Tu , Junfen Xu

MedComm ›› 2026, Vol. 7 ›› Issue (3) : e70654

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MedComm ›› 2026, Vol. 7 ›› Issue (3) :e70654 DOI: 10.1002/mco2.70654
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Clinical Application of Peripheral Blood Biomarkers for Solid Tumors
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Abstract

The growing emphasis on precision medicine in the management of solid tumors has underscored the limitations of traditional diagnostic approaches, which often lack sufficient sensitivity or rely on invasive procedures. In contrast, peripheral blood biomarkers provide a minimally invasive, dynamic, and potentially more accurate means for cancer detection and monitoring. The enhancement of detection technology has enabled the incorporation of an increasing number of biomarkers into exploratory clinical trials, which, in turn, have demonstrated immense clinical utility. However, numerous hurdles remain before these biomarkers can be applied in a real clinical setting. This review comprehensively summarizes the clinical utility of key blood-based biomarkers, including circulating tumor cells, circulating tumor DNA, extracellular vesicles, cell-free RNA, peripheral blood mononuclear cells, and proteins. We discuss their biological characteristics, detection methodologies, and recent advances in their clinical applications. Moreover, we highlight the emerging role of new technologies such as artificial intelligence (AI) in decoding complex data and facilitating clinical decision-making. It is expected to establish the overarching concept of the blood biomarker panel and to understand its comparative advantages, which are essential to realize its potential in precision oncology.

Keywords

blood biomarkers / machine learning / noninvasive tumor detection / precision oncology

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Xinru Tu, Mengyan Tu, Junfen Xu. Clinical Application of Peripheral Blood Biomarkers for Solid Tumors. MedComm, 2026, 7 (3) : e70654 DOI:10.1002/mco2.70654

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References

[1]

F. Bray, M. Laversanne, H. Sung, et al., “Global Cancer Statistics 2022: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA: A Cancer Journal for Clinicians 74, no. 3 (2024): 229–263.

[2]

C. Swanton, E. Bernard, C. Abbosh, et al., “Embracing Cancer Complexity: Hallmarks of Systemic Disease,” Cell 187, no. 7 (2024): 1589–1616.

[3]

X. Yang, C. Yang, S. Zhang, et al., “Precision Treatment in Advanced Hepatocellular Carcinoma,” Cancer Cell 42, no. 2 (2024): 180–197.

[4]

K. Chen, F. Yang, H. Shen, et al., “Individualized Tumor-Informed Circulating Tumor DNA Analysis for Postoperative Monitoring of Non-Small Cell Lung Cancer,” Cancer Cell 41, no. 10 (2023): 1749–1762.e6.

[5]

B. M. Lehrich, J. Zhang, S. P. Monga, et al., “Battle of the Biopsies: Role of Tissue and Liquid Biopsy in Hepatocellular Carcinoma,” Journal of Hepatology 80, no. 3 (2024): 515–530.

[6]

M. Nikanjam, S. Kato, and R. Kurzrock, “Liquid Biopsy: Current Technology and Clinical Applications,” Journal of Hematology & Oncology 15, no. 1 (2022): 131.

[7]

J. Lipkova, R. J. Chen, B. Chen, et al., “Artificial Intelligence for Multimodal Data Integration in Oncology,” Cancer Cell 40, no. 10 (2022): 1095–1110.

[8]

S. K. Yoo, C. W. Fitzgerald, B. A. Cho, et al., “Prediction of Checkpoint Inhibitor Immunotherapy Efficacy for Cancer Using Routine Blood Tests and Clinical Data,” Nature Medicine 31, no. 3 (2025): 869–880.

[9]

A. Ring, B. D. Nguyen-Sträuli, A. Wicki, et al., “Biology, Vulnerabilities and Clinical Applications of Circulating Tumour Cells,” Nature Reviews Cancer 23, no. 2 (2023): 95–111.

[10]

R. Lawrence, M. Watters, C. R. Davies, et al., “Circulating Tumour Cells for Early Detection of Clinically Relevant Cancer,” Nature Reviews Clinical oncology 20, no. 7 (2023): 487–500.

[11]

M. Merteroglu and M. M. Santoro, “Exploiting the Metabolic Vulnerability of Circulating Tumour Cells,” Trends in Cancer 10, no. 6 (2024): 541–556.

[12]

S. Sun, Q. Yang, D. Jiang, et al., “Nanobiotechnology Augmented Cancer Stem Cell Guided Management of Cancer: Liquid-Biopsy, Imaging, and Treatment,” Journal of Nanobiotechnology 22, no. 1 (2024): 176.

[13]

Q. Wang, B. Šabanović, A. Awada, et al., “Single-Cell Omics: A New Perspective for Early Detection of Pancreatic Cancer?,” European Journal of Cancer 190 (2023): 112940.

[14]

Q. Zhang, Y. Rong, K. Yi, et al., “Circulating Tumor Cells in Hepatocellular Carcinoma: Single-Cell Based Analysis, Preclinical Models, and Clinical Applications,” Theranostics 10, no. 26 (2020): 12060–12071.

[15]

A. Ntzifa and E. Lianidou, “Pre-Analytical Conditions and Implementation of Quality Control Steps in Liquid Biopsy Analysis,” Critical Reviews in Clinical Laboratory Sciences 60, no. 8 (2023): 573–594.

[16]

L. Bergmann, A. K. Afflerbach, T. Yuan, et al., “Lessons (to Be) Learned From Liquid Biopsies: Assessment of Circulating Cells and Cell-Free DNA in Cancer and Pregnancy-Acquired Microchimerism,” Seminars in Immunopathology 47, no. 1 (2025): 14.

[17]

D. J. Smit and K. Pantel, “Circulating Tumor Cells as Liquid Biopsy Markers in Cancer Patients,” Molecular Aspects of Medicine 96 (2024): 101258.

[18]

N. Feely, A. Wdowicz, A. Chevalier, et al., “Targeting Mucin Protein Enables Rapid and Efficient Ovarian Cancer Cell Capture: Role of Nanoparticle Properties in Efficient Capture and Culture,” Small 19, no. 18 (2023): e2207154.

[19]

G. Li, Y. Ji, Y. Wu, et al., “Multistage Microfluidic Cell Sorting Method and Chip Based on Size and Stiffness,” Biosensors & Bioelectronics 237 (2023): 115451.

[20]

C. Magnusson, P. Augustsson, E. Undvall Anand, et al., “Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters From Metastatic Prostate Cancer Patients,” Analytical Chemistry 96, no. 18 (2024): 6914–6921.

[21]

J. Wang, R. Dallmann, R. Lu, et al., “Flow Rate-Independent Multiscale Liquid Biopsy for Precision Oncology,” ACS Sens 8, no. 3 (2023): 1200–1210.

[22]

Y. Zhang, F. Zhang, Y. Song, et al., “Interfacial Polymerization Produced Magnetic Particles With Nano-Filopodia for Highly Accurate Liquid Biopsy in the Psa Gray Zone,” Advanced Materials 35, no. 48 (2023): e2303821.

[23]

C. Li, S. Yang, R. Li, et al., “Dual-Aptamer-Targeted Immunomagnetic Nanoparticles to Accurately Explore the Correlations Between Circulating Tumor Cells and Gastric Cancer,” ACS Applied Materials & Interfaces 14, no. 6 (2022): 7646–7658.

[24]

M. Bai, X. Tian, Z. Wang, et al., “Versatile Dynamic Bioactive Lubricant-Infused Surface for Effective Isolation of Circulating Tumor Cells,” Analytical Chemistry 95, no. 12 (2023): 5307–5315.

[25]

L. Chen, S. Luo, Z. Ge, et al., “Unbiased Enrichment of Circulating Tumor Cells via Dnazyme-Catalyzed Proximal Protein Biotinylation,” Nano Letters 22, no. 4 (2022): 1618–1625.

[26]

A. Mishra, S. B. Huang, T. Dubash, et al., “Tumor Cell-Based Liquid Biopsy Using High-Throughput Microfluidic Enrichment of Entire Leukapheresis Product,” Nature Communications 16, no. 1 (2025): 32.

[27]

D. Pirone, A. Montella, D. G. Sirico, et al., “Label-Free Liquid Biopsy Through the Identification of Tumor Cells by Machine Learning-Powered Tomographic Phase Imaging Flow Cytometry,” Scientific Reports 13, no. 1 (2023): 6042.

[28]

X. Guo, F. Lin, C. Yi, et al., “Deep Transfer Learning Enables Lesion Tracing of Circulating Tumor Cells,” Nature Communications 13, no. 1 (2022): 7687.

[29]

Z. Zhu, Y. Zhang, W. Zhang, et al., “High-Throughput Enrichment of Portal Venous Circulating Tumor Cells for Highly Sensitive Diagnosis of Ca19-9-Negative Pancreatic Cancer Patients Using Inertial Microfluidics,” Biosensors & Bioelectronics 259 (2024): 116411.

[30]

Y. He, Z. Zhan, L. Yan, et al., “Single-Cell Liquid Biopsy of Lung Cancer: Ultra-Simplified Efficient Enrichment of Circulating Tumor Cells and Hand-Held Fluorometer Portable Testing,” ACS Nano 18, no. 6 (2024): 5017–5028.

[31]

Y. Wang, X. Chen, X. Shen, et al., “Simplified Rapid Enrichment of Ctcs and Selective Recognition Prereduction Enable a Homogeneous Icp-Ms Liquid Biopsy Strategy of Lung Cancer,” Analytical Chemistry 95, no. 38 (2023): 14244–14252.

[32]

W. Liu, Y. Wang, P. Jiang, et al., “Dnazyme and Controllable Cholesterol Stacking DNA Machine Integrates Dual-Target Recognition Ctcs Enable Homogeneous Liquid Biopsy of Breast Cancer,” Biosensors & Bioelectronics 261 (2024): 116493.

[33]

N. H. Stoecklein, G. Fluegen, R. Guglielmi, et al., “Ultra-Sensitive Ctc-Based Liquid Biopsy for Pancreatic Cancer Enabled by Large Blood Volume Analysis,” Molecular Cancer 22, no. 1 (2023): 181.

[34]

Z. Niu, M. Kozminsky, K. C. Day, et al., “Characterization of Circulating Tumor Cells in Patients With Metastatic Bladder Cancer Utilizing Functionalized Microfluidics,” Neoplasia 57 (2024): 101036.

[35]

A. C. de Jong, K. T. Isebia, S. W. Ling, et al., “Liquid Biopsies for Early Response Evaluation of Radium-223 in Metastatic Prostate Cancer,” JCO Precision Oncology 7 (2023): e2300156.

[36]

M. N. Sharifi, J. M. Sperger, A. K. Taylor, et al., “High-Purity Ctc Rna Sequencing Identifies Prostate Cancer Lineage Phenotypes Prognostic for Clinical Outcomes,” Cancer Discovery 15, no. 5 (2025): 969–987.

[37]

I. Heidrich, B. Deitert, S. Werner, et al., “Liquid Biopsy for Monitoring of Tumor Dormancy and Early Detection of Disease Recurrence in Solid Tumors,” Cancer and Metastasis Reviews 42, no. 1 (2023): 161–182.

[38]

Q. Zhang, X. Zhang, Z. Lv, et al., “Dynamically Monitoring Minimal Residual Disease Using Circulating Tumour Cells to Predict the Recurrence of Early-Stage Lung Adenocarcinoma,” Journal of Hematology & Oncology 17, no. 1 (2024): 114.

[39]

L. Zhao, L. Jiang, Y. Liu, et al., “Integrated Analysis of Circulating Tumour Cells and Circulating Tumour DNA to Detect Minimal Residual Disease in Hepatocellular Carcinoma,” Clinical and Translational Medicine 12, no. 4 (2022): e793.

[40]

A. F. Espinoza, P. Kureti, R. H. Patel, et al., “An Indocyanine Green-Based Liquid Biopsy Test for Circulating Tumor Cells for Pediatric Liver Cancer,” Hepatol Commun 8, no. 6 (2024): e0435.

[41]

L. Chen, W. Zhou, Z. Ye, et al., “Predictive Value of Circulating Tumor Cells Based on Subtraction Enrichment for Recurrence Risk in Stage Ii Colorectal Cancer,” ACS Applied Materials & Interfaces 14, no. 31 (2022): 35389–35399.

[42]

A. Matikas, A. Kotsakis, S. Apostolaki, et al., “Detection of Circulating Tumour Cells Before and Following Adjuvant Chemotherapy and Long-Term Prognosis of Early Breast Cancer,” British Journal of Cancer 126, no. 11 (2022): 1563–1569.

[43]

Y. Liu, B. Zhang, X. Wu, et al., “A Facile Liquid Biopsy Assay for Highly Efficient Ctcs Capture and Reagent-Less Monitoring of Immune Checkpoint Pd-L1 Expression on Ctcs With Non-Small Cell Lung Cancer Patients,” Biosensors & Bioelectronics 275 (2025): 117236.

[44]

M. Ruiz-Vico, D. Wetterskog, F. Orlando, et al., “Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel With or Without Enzalutamide: A Biomarker Study of the Preside Phase 3b Trial,” European Urology Oncology 8, no. 1 (2025): 135–144.

[45]

K. M. Mahuron and Y. Fong, “Applications of Liquid Biopsy for Surgical Patients With Cancer: A Review,” JAMA Surg 159, no. 1 (2024): 96–103.

[46]

Y. Han, D. Wang, L. Peng, et al., “Single-Cell Sequencing: A Promising Approach for Uncovering the Mechanisms of Tumor Metastasis,” Journal Of Hematology & Oncology 15, no. 1 (2022): 59.

[47]

M. L. De Angelis, F. Francescangeli, C. Nicolazzo, et al., “An Organoid Model of Colorectal Circulating Tumor Cells With Stem Cell Features, Hybrid Emt State and Distinctive Therapy Response Profile,” Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022): 86.

[48]

R. Würth, E. Donato, L. L. Michel, et al., “Circulating Tumor Cell Plasticity Determines Breast Cancer Therapy Resistance via Neuregulin 1-Her3 Signaling,” Nature Cancer 6, no. 1 (2025): 67–85.

[49]

N. Swarup, H. Y. Leung, I. Choi, et al., “Cell-Free DNA: Features and Attributes Shaping the Next Frontier in Liquid Biopsy,” Molecular Diagnosis & Therapy 29, no. 3 (2025): 277–290.

[50]

P. Stejskal, H. Goodarzi, J. Srovnal, et al., “Circulating Tumor Nucleic Acids: Biology, Release Mechanisms, and Clinical Relevance,” Molecular Cancer 22, no. 1 (2023): 15.

[51]

C. Li, J. Shao, P. Li, et al., “Circulating Tumor DNA as Liquid Biopsy in Lung Cancer: Biological Characteristics and Clinical Integration,” Cancer Letters 577 (2023): 216365.

[52]

A. Bartolomucci, M. Nobrega, T. Ferrier, et al., “Circulating Tumor DNA to Monitor Treatment Response in Solid Tumors and Advance Precision Oncology,” NPJ Precis Oncol 9, no. 1 (2025): 84.

[53]

D. Ciardiello, L. Boscolo Bielo, S. Napolitano, et al., “Comprehensive Genomic Profiling by Liquid Biopsy Captures Tumor Heterogeneity and Identifies Cancer Vulnerabilities in Patients With Ras/Braf(V600e) Wild-Type Metastatic Colorectal Cancer in the Capri 2-Goim Trial,” Annals of Oncology 35, no. 12 (2024): 1105–1115.

[54]

M. G. White, M. A. Zeineddine, E. A. Fallon, et al., “The Landscape of Ctdna in Appendiceal Adenocarcinoma,” Clinical Cancer Research 31, no. 3 (2025): 551–560.

[55]

R. Behrouzi, A. Clipson, K. L. Simpson, et al., “Cell-Free and Extrachromosomal DNA Profiling of Small Cell Lung Cancer,” Trends in Molecular Medicine 31, no. 1 (2025): 64–78.

[56]

L. Bonstingl, C. Skofler, C. Ulz, et al., “Clinical Application of Iso and Cen/Ts Standards for Liquid Biopsies-Information Everybody Wants but Nobody Wants to Pay for,” Clinical Chemistry 70, no. 9 (2024): 1140–1150.

[57]

J. B. Iorgulescu, T. Blewett, K. Xiong, et al., “Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients,” Clinical Chemistry 71, no. 1 (2025): 215–225.

[58]

L. Fu, X. Zhou, X. Zhang, et al., “Circulating Tumor DNA in Lymphoma: Technologies and Applications,” Journal of Hematology & Oncology 18, no. 1 (2025): 29.

[59]

R. Li, L. Di, J. Li, et al., “A Body Map of Somatic Mutagenesis in Morphologically Normal Human Tissues,” Nature 597, no. 7876 (2021): 398–403.

[60]

B. C. Park, J. O. Soh, H. J. Choi, et al., “Ultrasensitive and Rapid Circulating Tumor DNA Liquid Biopsy Using Surface-Confined Gene Amplification on Dispersible Magnetic Nano-Electrodes,” ACS Nano 18, no. 20 (2024): 12781–12794.

[61]

N. Bellassai, R. D'Agata, E. Giordani, et al., “A Novel Method for Detecting Genetic Biomarkers in Blood-Based Liquid Biopsies Using Surface Plasmon Resonance Imaging and Magnetic Beads Shows Promise in Cancer Diagnosis and Monitoring,” Talanta 286 (2025): 127543.

[62]

H. Zhang, H. Gao, W. Mu, et al., “Electrochemical-Fluorescent Bimodal Biosensor Based on Dual Crispr-Cas12a Multiple Cascade Amplification for Ctdna Detection,” Analytical Chemistry 96, no. 34 (2024): 14028–14035.

[63]

J. Dong, X. Li, C. Hou, et al., “A Novel Crispr/Cas12a-Mediated Ratiometric Dual-Signal Electrochemical Biosensor for Ultrasensitive and Reliable Detection of Circulating Tumor Deoxyribonucleic Acid,” Analytical Chemistry 96, no. 18 (2024): 6930–6939.

[64]

T. Liang, X. Qin, Y. Zhang, et al., “Crispr/Dcas9-Mediated Specific Molecular Assembly Facilitates Genotyping of Mutant Circulating Tumor DNA,” Analytical Chemistry 95, no. 44 (2023): 16305–16314.

[65]

E. Y. Stutheit-Zhao, E. Sanz-Garcia, Z. A. Liu, et al., “Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors,” Cancer Discovery 14, no. 6 (2024): 1048–1063.

[66]

T. H. Hong, S. Hwang, A. Dasgupta, et al., “Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage Nsclc,” Journal of Thoracic Oncology 19, no. 11 (2024): 1512–1524.

[67]

X. L. Cui, J. Nie, H. Zhu, et al., “Labs: Linear Amplification-Based Bisulfite Sequencing for Ultrasensitive Cancer Detection From Cell-Free DNA,” Genome Biology 25, no. 1 (2024): 157.

[68]

X. Hua, H. Zhou, H. C. Wu, et al., “Tumor Detection by Analysis of both Symmetric- and Hemi-Methylation of Plasma Cell-Free DNA,” Nature Communications 15, no. 1 (2024): 6113.

[69]

D. V. Vavoulis, A. Cutts, N. Thota, et al., “Multimodal Cell-Free DNA Whole-Genome Taps Is Sensitive and Reveals Specific Cancer Signals,” Nature Communications 16, no. 1 (2025): 430.

[70]

T. Moser, S. Kühberger, I. Lazzeri, et al., “Bridging Biological Cfdna Features and Machine Learning Approaches,” Trends in Genetics 39, no. 4 (2023): 285–307.

[71]

W. H. A. Tsui, S. C. Ding, P. Jiang, et al., “Artificial Intelligence and Machine Learning in Cell-Free-DNA-Based Diagnostics,” Genome Research 35, no. 1 (2025): 1–19.

[72]

X. Zhang, J. Chen, Y. Wang, et al., “Cfmethylpre: Deep Transfer Learning Enhances Cancer Detection Based on Circulating Cell-Free DNA Methylation Profiling,” Brief Bioinform 26, no. 3 (2025): bbaf303.

[73]

C. D. Rolfo, R. W. Madison, L. W. Pasquina, et al., “Measurement of Ctdna Tumor Fraction Identifies Informative Negative Liquid Biopsy Results and Informs Value of Tissue Confirmation,” Clinical Cancer Research 30, no. 11 (2024): 2452–2460.

[74]

A. M. Conway, S. P. Pearce, A. Clipson, et al., “A Cfdna Methylation-Based Tissue-of-Origin Classifier for Cancers of Unknown Primary,” Nature Communications 15, no. 1 (2024): 3292.

[75]

A. V. Annapragada, N. Niknafs, J. R. White, et al., “Genome-Wide Repeat Landscapes in Cancer and Cell-Free DNA,” Science Translational Medicine 16, no. 738 (2024): eadj9283.

[76]

P. Yu, P. Chen, M. Wu, et al., “Multi-Dimensional Cell-Free DNA-Based Liquid Biopsy for Sensitive Early Detection of Gastric Cancer,” Genome Medicine 16, no. 1 (2024): 79.

[77]

G. A. Herrgott, J. M. Snyder, R. She, et al., “Detection of Diagnostic and Prognostic Methylation-Based Signatures in Liquid Biopsy Specimens From Patients With Meningiomas,” Nature Communications 14, no. 1 (2023): 5669.

[78]

G. Li, Y. Zhang, K. Li, et al., “Transformer-Based Ai Technology Improves Early Ovarian Cancer Diagnosis Using Cfdna Methylation Markers,” Cell Reports Medicine 5, no. 8 (2024): 101666.

[79]

D. Guo, A. Huang, J. Sun, et al., “The Genomic and Epigenomic Abnormalities of Plasma Cfdna as Liquid Biopsy Biomarkers to Detect Hepatocellular Carcinoma: A Multicenter Cohort Study,” Journal of hematology & oncology 18, no. 1 (2025): 94.

[80]

S. Heeke, C. M. Gay, M. R. Estecio, et al., “Tumor- and Circulating-Free DNA Methylation Identifies Clinically Relevant Small Cell Lung Cancer Subtypes,” Cancer Cell 42, no. 2 (2024): 225–237.e5.

[81]

S. Xu, J. Luo, W. Tang, et al., “Detecting Pulmonary Malignancy Against Benign Nodules Using Noninvasive Cell-Free DNA Fragmentomics Assay,” ESMO Open 9, no. 8 (2024): 103595.

[82]

M. Yang, Y. Zhao, C. Li, et al., “Multimodal Integration of Liquid Biopsy and Radiology for the Noninvasive Diagnosis of Gallbladder Cancer and Benign Disorders,” Cancer Cell 43, no. 3 (2025): 398–412.e4.

[83]

K. Pantel and C. Alix-Panabières, “Minimal Residual Disease as a Target for Liquid Biopsy in Patients With Solid Tumours,” Nature reviews Clinical oncology 22, no. 1 (2025): 65–77.

[84]

M. Zhang, H. Yang, T. Fu, et al., “Liquid Biopsy: Circulating Tumor DNA Monitors Neoadjuvant Chemotherapy Response and Prognosis in Stage Ii/Iii Gastric Cancer,” Mol Oncol 17, no. 9 (2023): 1930–1942.

[85]

S. Marchisio, A. A. Ricci, G. Roccuzzo, et al., “Monitoring Circulating Tumor DNA Liquid Biopsy in Stage Iii Braf-Mutant Melanoma Patients Undergoing Adjuvant Treatment,” Journal of translational medicine 22, no. 1 (2024): 1074.

[86]

S. Mo, L. Ye, D. Wang, et al., “Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to Iii Colorectal Cancer via Circulating Tumor DNA Methylation,” JAMA oncology 9, no. 6 (2023): 770–778.

[87]

S. Slater, A. Bryant, M. Aresu, et al., “Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients With Early Colorectal Cancer From the Uk Tracc Part B Study,” Clinical Cancer Research 30, no. 16 (2024): 3459–3469.

[88]

Y. Nakamura, J. Watanabe, N. Akazawa, et al., “Ctdna-Based Molecular Residual Disease and Survival in Resectable Colorectal Cancer,” Nature Medicine 30, no. 11 (2024): 3272–3283.

[89]

B. Audinot, D. Drubay, N. Gaspar, et al., “Ctdna Quantification Improves Estimation of Outcomes in Patients With High-Grade Osteosarcoma: A Translational Study From the Os2006 Trial,” Annals of Oncology: Official Journal of the European Society for Medical Oncology 35, no. 6 (2024): 559–568.

[90]

I. Nordentoft, S. V. Lindskrog, K. Birkenkamp-Demtröder, et al., “Whole-Genome Mutational Analysis for Tumor-Informed Detection of Circulating Tumor DNA in Patients With Urothelial Carcinoma,” European Urology 86, no. 4 (2024): 301–311.

[91]

A. Huebner, J. R. M. Black, F. Sarno, et al., “Act-Discover: Identifying Karyotype Heterogeneity in Pancreatic Cancer Evolution Using Ctdna,” Genome Medicine 15, no. 1 (2023): 27.

[92]

P. Soberanis Pina, K. Clemens, A. Bubie, et al., “Genomic Landscape of Ctdna and Real-World Outcomes in Advanced Endometrial Cancer,” Clinical Cancer Research 30, no. 24 (2024): 5657–5665.

[93]

C. Abbosh, A. M. Frankell, T. Harrison, et al., “Tracking Early Lung Cancer Metastatic Dissemination in Tracerx Using Ctdna,” Nature 616, no. 7957 (2023): 553–562.

[94]

P. S. Chauhan, I. Alahi, S. Sinha, et al., “Genomic and Epigenomic Analysis of Plasma Cell-Free DNA Identifies Stemness Features Associated With Worse Survival in Lethal Prostate Cancer,” Clinical Cancer Research 31, no. 1 (2025): 151–163.

[95]

G. Beinse, B. Borghese, M. Métairie, et al., “Highly Specific Droplet-Digital Pcr Detection of Universally Methylated Circulating Tumor DNA in Endometrial Carcinoma,” Clinical Chemistry 68, no. 6 (2022): 782–793.

[96]

S. Ma, J. Y. Jiang, R. B. Kim, et al., “Circulating Tumor DNA Predicts Venous Thromboembolism in Patients With Cancers,” Journal of Thrombosis and Haemostasis 23, no. 1 (2025): 139–148.

[97]

J. Jee, A. R. Brannon, R. Singh, et al., “DNA Liquid Biopsy-Based Prediction of Cancer-Associated Venous Thromboembolism,” Nature Medicine 30, no. 9 (2024): 2499–2507.

[98]

F. Campo, O. Iocca, F. Paolini, et al., “The Landscape of Circulating Tumor Hpv DNA and Ttmv-Hpvdna for Surveillance of Hpv-Oropharyngeal Carcinoma: Systematic Review and Meta-Analysis,” Journal of Experimental & Clinical Cancer Research 43, no. 1 (2024): 215.

[99]

J. Lv, L. X. Xu, Z. X. Li, et al., “Longitudinal on-Treatment Circulating Tumor DNA as a Biomarker for Real-Time Dynamic Risk Monitoring in Cancer Patients: The Ep-Season Study,” Cancer Cell 42, no. 8 (2024): 1401–1414.e4.

[100]

T. Powles, Y. H. Chang, Y. Yamamoto, et al., “Pembrolizumab for Advanced Urothelial Carcinoma: Exploratory Ctdna Biomarker Analyses of the Keynote-361 Phase 3 Trial,” Nature Medicine 30, no. 9 (2024): 2508–2516.

[101]

J. Zafra, J. L. Onieva, J. Oliver, et al., “Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer,” International Journal of Molecular Sciences 25, no. 8 (2024): 4533.

[102]

L. Sivapalan, J. C. Murray, J. V. Canzoniero, et al., “Liquid Biopsy Approaches to Capture Tumor Evolution and Clinical Outcomes During Cancer Immunotherapy,” Journal for ImmunoTherapy of Cancer 11, no. 1 (2023): e005924.

[103]

X. Han, J. Guo, L. Li, et al., “Sintilimab Combined With Anlotinib and Chemotherapy as Second-Line or Later Therapy in Extensive-Stage Small Cell Lung Cancer: A Phase Ii Clinical Trial,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 241.

[104]

C. Schroeder, S. Gatidis, O. Kelemen, et al., “Tumour-Informed Liquid Biopsies to Monitor Advanced Melanoma Patients Under Immune Checkpoint Inhibition,” Nature Communications 15, no. 1 (2024): 8750.

[105]

J. Tie, Y. Wang, S. N. Lo, et al., “Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage Ii Colon Cancer: 5-Year Outcomes of the Randomized Dynamic Trial,” Nature Medicine 31, no. 5 (2025): 1509–1518.

[106]

T. Powles, Z. J. Assaf, V. Degaonkar, et al., “Updated Overall Survival by Circulating Tumor DNA Status From the Phase 3 Imvigor010 Trial: Adjuvant Atezolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma,” European Urology 85, no. 2 (2024): 114–122.

[107]

J. Xu, R. Wan, Y. Cai, et al., “Circulating Tumor DNA-Based Stratification Strategy for Chemotherapy plus Pd-1 Inhibitor in Advanced Non-Small-Cell Lung Cancer,” Cancer Cell 42, no. 9 (2024): 1598–1613.e4.

[108]

Y. Nakamura, H. Ozaki, M. Ueno, et al., “Targeted Therapy Guided by Circulating Tumor DNA Analysis in Advanced Gastrointestinal Tumors,” Nature Medicine 31, no. 1 (2025): 165–175.

[109]

D. Triner, R. P. Graf, R. W. Madison, et al., “Durable Benefit From Poly(Adp-Ribose) Polymerase Inhibitors in Metastatic Prostate Cancer in Routine Practice: Biomarker Associations and Implications for Optimal Clinical Next-Generation Sequencing Testing,” ESMO Open 9, no. 9 (2024): 103684.

[110]

S. Siena, K. Raghav, T. Masuishi, et al., “Her2-Related Biomarkers Predict Clinical Outcomes With Trastuzumab Deruxtecan Treatment in Patients With Her2-Expressing Metastatic Colorectal Cancer: Biomarker Analyses of Destiny-Crc01,” Nature Communications 15, no. 1 (2024): 10213.

[111]

A. González-Medina, M. Vila-Casadesús, M. Gomez-Rey, et al., “152 Clinical Value of Liquid Biopsy in Patients With Fgfr2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy,” Clinical Cancer Research 30, no. 19 (2024): 4491–4504.

[112]

S. Weiss, P. Lamy, M. Rusan, et al., “Exploring the Tumor Genomic Landscape of Aggressive Prostate Cancer by Whole-Genome Sequencing of Tissue or Liquid Biopsies,” International Journal of Cancer 155, no. 2 (2024): 298–313.

[113]

I. Vanni, L. Pastorino, V. Andreotti, et al., “Combining Germline, Tissue and Liquid Biopsy Analysis by Comprehensive Genomic Profiling to Improve the Yield of Actionable Variants in a Real-World Cancer Cohort,” Journal of translational medicine 22, no. 1 (2024): 462.

[114]

J. A. Welsh, D. C. I. Goberdhan, L. O'Driscoll, et al., “Minimal Information for Studies of Extracellular Vesicles (Misev2023): From Basic to Advanced Approaches,” Journal of Extracellular Vesicles 13, no. 2 (2024): e12404.

[115]

C. Yang, Y. Xue, Y. Duan, et al., “Extracellular Vesicles and Their Engineering Strategies, Delivery Systems, and Biomedical Applications,” Journal of Controlled Release: Official Journal of the Controlled Release Society 365 (2024): 1089–1123.

[116]

I. A. Batista, J. C. Machado, and S. A. Melo, “Advances in Exosomes Utilization for Clinical Applications in Cancer,” Trends in cancer 10, no. 10 (2024): 947–968.

[117]

R. Kalluri and K. M. McAndrews, “The Role of Extracellular Vesicles in Cancer,” Cell 186, no. 8 (2023): 1610–1626.

[118]

T. Tsering, A. Nadeau, T. Wu, et al., “Extracellular Vesicle-Associated DNA: Ten Years Since Its Discovery in Human Blood,” Cell death & disease 15, no. 9 (2024): 668.

[119]

M. Samuels, W. Jones, B. Towler, et al., “The Role of Non-Coding Rnas in Extracellular Vesicles in Breast Cancer and Their Diagnostic Implications,” Oncogene 42, no. 41 (2023): 3017–3034.

[120]

H. Chen, B. Pang, C. Zhou, et al., “Prostate Cancer-Derived Small Extracellular Vesicle Proteins: The Hope in Diagnosis, Prognosis, and Therapeutics,” Journal of Nanobiotechnology 21, no. 1 (2023): 480.

[121]

M. A. Hamed, V. Wasinger, Q. Wang, et al., “Prostate Cancer-Derived Extracellular Vesicles Metabolic Biomarkers: Emerging Roles for Diagnosis and Prognosis,” Journal of Controlled Release 371 (2024): 126–145.

[122]

J. Wu, Q. Dou, M. Mao, et al., “Single Extracellular Vesicle Imaging via Rolling Circle Amplification-Expansion Microscopy,” Nature Communications 16, no. 1 (2025): 7498.

[123]

S. Rayamajhi, J. Sipes, A. L. Tetlow, et al., “Extracellular Vesicles as Liquid Biopsy Biomarkers Across the Cancer Journey: From Early Detection to Recurrence,” Clinical Chemistry 70, no. 1 (2024): 206–219.

[124]

D. J. Beetler, D. N. Di Florio, K. A. Bruno, et al., “Extracellular Vesicles as Personalized Medicine,” Molecular Aspects of Medicine 91 (2023): 101155.

[125]

H. Tang, D. Yu, J. Zhang, et al., “The New Advance of Exosome-Based Liquid Biopsy for Cancer Diagnosis,” Journal of Nanobiotechnology 22, no. 1 (2024): 610.

[126]

S. Gandham, X. Su, J. Wood, et al., “Technologies and Standardization in Research on Extracellular Vesicles,” Trends in Biotechnology 38, no. 10 (2020): 1066–1098.

[127]

J. Nouvel, G. Bustos-Quevedo, T. Prinz, et al., “Separation of Small Extracellular Vesicles (Sev) From Human Blood by Superose 6 Size Exclusion Chromatography,” Journal of Extracellular Vesicles 13, no. 10 (2024): e70008.

[128]

S. Wang, Y. He, T. Tian, et al., “Nanoarray Enabled Size-Dependent Isolation and Proteomics Profiling of Small Extracellular Vesicle Subpopulations Toward Accurate Cancer Diagnosis and Prognosis,” Analytical Chemistry 95, no. 41 (2023): 15276–15285.

[129]

M. H. Jeong, T. Son, Y. K. Tae, et al., “Plasmon-Enhanced Single Extracellular Vesicle Analysis for Cholangiocarcinoma Diagnosis,” Advanced Science (Weinh) 10, no. 8 (2023): e2205148.

[130]

S. Lian, Q. Wang, Y. Liu, et al., “Multi-Targeted Nanoarrays for Early Broad-Spectrum Detection of Lung Cancer Based on Blood Biopsy of Tumor Exosomes,” Talanta 276 (2024): 126270.

[131]

F. Bu, X. Shen, H. Zhan, et al., “Efficient Metabolomics Profiling From Plasma Extracellular Vesicles Enables Accurate Diagnosis of Early Gastric Cancer,” Journal of the American Chemical Society 147, no. 10 (2025): 8672–8686.

[132]

A. Gori, R. Frigerio, P. Gagni, et al., “Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan-Vesicular Affinity Probes,” Advanced Science (Weinh) 11, no. 29 (2024): e2400533.

[133]

C. V. Pham, R. Chowdhury, S. Patel, et al., “An Aptamer-Guided Fluorescence Polarisation Platform for Extracellular Vesicle Liquid Biopsy,” Journal of Extracellular Vesicles 13, no. 9 (2024): e12502.

[134]

Z. Zong, X. Liu, Z. Ye, et al., “A Double-Switch Phlip System Enables Selective Enrichment of Circulating Tumor Microenvironment-Derived Extracellular Vesicles,” PNAS 120, no. 2 (2023): e2214912120.

[135]

M. Lan, D. Wu, C. Cheng, et al., “Small Extracellular Vesicles Detection by Dielectrophoresis-Based Microfluidic Chip Filled With Transparent Antibody-Conjugated Microbeads for Breast Cancer Diagnosis,” Analytical Chemistry 97, no. 10 (2025): 5678–5687.

[136]

S. Y. Leong, W. W. Lok, K. Y. Goh, et al., “High-Throughput Microfluidic Extraction of Platelet-Free Plasma for Microrna and Extracellular Vesicle Analysis,” ACS Nano 18, no. 8 (2024): 6623–6637.

[137]

L. Ding, X. Liu, Z. Zhang, et al., “Magnetic-Nanowaxberry-Based Microfluidic Exosic for Affinity and Continuous Separation of Circulating Exosomes towards Cancer Diagnosis,” Lab on A Chip 23, no. 6 (2023): 1694–1702.

[138]

R. P. Carney, R. R. Mizenko, B. T. Bozkurt, et al., “Harnessing Extracellular Vesicle Heterogeneity for Diagnostic and Therapeutic Applications,” Nature Nanotechnology 20, no. 1 (2025): 14–25.

[139]

Y. Liu, M. Li, H. Liu, et al., “Cancer Diagnosis Using Label-Free Sers-Based Exosome Analysis,” Theranostics 14, no. 5 (2024): 1966–1981.

[140]

Q. He, H. J. Koster, J. O'Sullivan, et al., “Integration of Label-Free Surface Enhanced Raman Spectroscopy (Sers) of Extracellular Vesicles (Evs) With Raman Tagged Labels to Enhance Ovarian Cancer Diagnostics,” Biosensors & Bioelectronics 288 (2025): 117800.

[141]

Z. Liu, W. Zhang, X. Zhang, et al., “Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer,” Analytical Chemistry 95, no. 2 (2023): 1095–1105.

[142]

M. Fu, P. Zhou, W. Sheng, et al., “Magnetically Controlled Photothermal, Colorimetric, and Fluorescence Trimode Assay for Gastric Cancer Exosomes Based on Acid-Induced Decomposition of Cp/Mn-Pba Dsnbs,” Analytical Chemistry 96, no. 10 (2024): 4213–4223.

[143]

Q. Liu, Q. Zhang, Z. Yao, et al., “Pushing Forward the DNA Walkers in Connection With Tumor-Derived Extracellular Vesicles,” International Journal of Nanomedicine 19 (2024): 6231–6252.

[144]

M. Park, C. H. Lee, H. Noh, et al., “High-Precision Extracellular-Vesicle Isolation-Analysis Integrated Platform for Rapid Cancer Diagnosis Directly From Blood Plasma,” Biosensors & Bioelectronics 267 (2025): 116863.

[145]

E. M. Clarissa, S. Kumar, J. Park, et al., “Digital Profiling of Tumor Extracellular Vesicle-Associated Rnas Directly From Unprocessed Blood Plasma,” ACS Nano 19, no. 5 (2025): 5526–5538.

[146]

Y. Zhang, X. Qin, Z. Xu, et al., “Electric Field-Resistant Bubble-Enhanced Wash-Free Profiling of Extracellular Vesicle Surface Markers,” ACS Nano 19, no. 8 (2025): 8093–8107.

[147]

X. Li, Y. Liu, Y. Fan, et al., “Advanced Nanoencapsulation-Enabled Ultrasensitive Analysis: Unraveling Tumor Extracellular Vesicle Subpopulations for Differential Diagnosis of Hepatocellular Carcinoma via DNA Cascade Reactions,” ACS Nano 18, no. 17 (2024): 11389–11403.

[148]

X. Zhao, X. Liu, T. Chen, et al., “Fully Integrated Centrifugal Microfluidics for Rapid Exosome Isolation, Glycan Analysis, and Point-of-Care Diagnosis,” ACS Nano 19, no. 9 (2025): 8948–8965.

[149]

Y. He, X. Zeng, Y. Xiong, et al., “Portable Aptasensor Based on Parallel Rolling Circle Amplification for Tumor-Derived Exosomes Liquid Biopsy,” Advanced Science (Weinh) 11, no. 32 (2024): e2403371.

[150]

Z. Ding, Y. Wei, F. Han, et al., “DNA-Driven Photothermal Amplification Transducer for Highly Sensitive Visual Determination of Extracellular Vesicles,” ACS Sens 8, no. 6 (2023): 2282–2289.

[151]

L. Veliz, T. T. Cooper, I. Grenier-Pleau, et al., “Tandem Sers and Ms/Ms Profiling of Plasma Extracellular Vesicles for Early Ovarian Cancer Biomarker Discovery,” ACS sensors 9, no. 1 (2024): 272–282.

[152]

J. W. Clancy and C. D'Souza-Schorey, “Tumor-Derived Extracellular Vesicles: Multifunctional Entities in the Tumor Microenvironment,” Annual Review of Pathology 18 (2023): 205–229.

[153]

F. L. Ricklefs, K. Wollmann, A. Salviano-Silva, et al., “Circulating Extracellular Vesicles as Biomarker for Diagnosis, Prognosis, and Monitoring in Glioblastoma Patients,” Neuro-Oncology 26, no. 7 (2024): 1280–1291.

[154]

A. Zhang, Q. Gao, C. Tian, et al., “Liquid Biopsy in Lung Cancer: Nano-Flow Cytometry Detection of Non-Small Cell Lung Cancer in Blood,” Laboratory Investigation 104, no. 12 (2024): 102151.

[155]

Y. Lu, X. Li, Y. Liu, et al., “Novel Molecular Aptamer Beacon for the Specific Simultaneous Analysis of Circulating Tumor Cells and Exosomes of Colorectal Cancer Patients,” Analytical Chemistry 95, no. 2 (2023): 1251–1261.

[156]

V. De Giorgis, E. Barberis, and M. Manfredi, “Extracellular Vesicles Proteins for Early Cancer Diagnosis: From Omics to Biomarkers,” Seminars in Cancer Biology 104-105 (2024): 18–31.

[157]

M. Bocchetti, A. Luce, C. Iannarone, et al., “Exosomes Multiplex Profiling, a Promising Strategy for Early Diagnosis of Laryngeal Cancer,” Journal of translational medicine 22, no. 1 (2024): 582.

[158]

Y. Feng, Y. Yang, Y. Xiao, et al., “Multi-Parameter Inputted Logic-Gating on Aptamer-Encoded Extracellular Vesicles for Colorectal Cancer Diagnosis,” Analytical Chemistry 95, no. 2 (2023): 1132–1139.

[159]

A. Jo, A. Green, J. E. Medina, et al., “Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection,” Advanced Science (Weinheim, Baden-Wurttemberg, Germany) 10, no. 27 (2023): e2301930.

[160]

Z. Andreu, M. R. Hidalgo, E. Masiá, et al., “Comparative Profiling of Whole-Cell and Exosome Samples Reveals Protein Signatures That Stratify Breast Cancer Subtypes,” Cellular and Molecular Life Sciences 81, no. 1 (2024): 363.

[161]

H. Yin, J. Xie, S. Xing, et al., “Machine Learning-Based Analysis Identifies and Validates Serum Exosomal Proteomic Signatures for the Diagnosis of Colorectal Cancer,” Cell Reports Medicine 5, no. 8 (2024): 101689.

[162]

X. Zhang, Y. Jia, Z. Li, et al., “Microfluidic Biochip-Based Multiplexed Profiling of Small Extracellular Vesicles Proteins Integrated With Machine Learning for Early Disease Diagnosis,” Advanced Science (Weinh) 12, no. 37 (2025): e06167.

[163]

J. Chang, L. Zhang, Z. Li, et al., “Exosomal Non-Coding Rnas (Ncrnas) as Potential Biomarkers in Tumor Early Diagnosis,” Biochimica Et Biophysica Acta Reviews on Cancer 1879, no. 6 (2024): 189188.

[164]

T. Wu, Y. Dai, Y. Xu, et al., “Exosomepurity: Tumour Purity Deconvolution in Serum Exosomes Based on Mirna Signatures,” Brief Bioinform 24, no. 3 (2023): bbad119.

[165]

S. M. Batool, A. K. Escobedo, T. Hsia, et al., “Clinical Utility of a Blood Based Assay for the Detection of Idh1.R132h-Mutant Gliomas,” Nature Communications 15, no. 1 (2024): 7074.

[166]

N. Wen, D. Peng, X. Xiong, et al., “Cholangiocarcinoma Combined With Biliary Obstruction: An Exosomal Circrna Signature for Diagnosis and Early Recurrence Monitoring,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 107.

[167]

X. Sun, B. Chen, Y. Shan, et al., “Lectin Microarray Based Glycan Profiling of Exosomes for Dynamic Monitoring of Colorectal Cancer Progression,” Analytica Chimica Acta 1316 (2024): 342819.

[168]

Q. Zhou, X. Niu, Z. Zhang, et al., “Glycan Profiling in Small Extracellular Vesicles With a Sers Microfluidic Biosensor Identifies Early Malignant Development in Lung Cancer,” Advanced Science (Weinh) 11, no. 33 (2024): e2401818.

[169]

J. Penders, A. Nagelkerke, E. M. Cunnane, et al., “Single Particle Automated Raman Trapping Analysis of Breast Cancer Cell-Derived Extracellular Vesicles as Cancer Biomarkers,” ACS nano 15, no. 11 (2021): 18192–18205.

[170]

S. Premachandran, R. Haldavnekar, S. Ganesh, et al., “Self-Functionalized Superlattice Nanosensor Enables Glioblastoma Diagnosis Using Liquid Biopsy,” ACS Nano 17, no. 20 (2023): 19832–19852.

[171]

C. Zhai, F. Xie, J. Xu, et al., “Correlation Between Membrane Proteins and Sizes of Extracellular Vesicles and Particles: A Potential Signature for Cancer Diagnosis,” Journal of Extracellular Vesicles 12, no. 12 (2023): e12391.

[172]

D. Zhong, Z. Wang, Z. Ye, et al., “Cancer-Derived Exosomes as Novel Biomarkers in Metastatic Gastrointestinal Cancer,” Molecular cancer 23, no. 1 (2024): 67.

[173]

J. Zhang, D. Yu, C. Ji, et al., “Exosomal Mir-4745-5p/3911 From N2-Polarized Tumor-Associated Neutrophils Promotes Gastric Cancer Metastasis by Regulating Slit2,” Molecular cancer 23, no. 1 (2024): 198.

[174]

S. Premachandran, I. Shreshtha, K. Venkatakrishnan, et al., “Detection of Brain Metastases From Blood Using Brain Nanomet Sensor: Extracellular Vesicles as a Dynamic Marker for Metastatic Brain Tumors,” Biosensors & Bioelectronics 269 (2025): 116968.

[175]

K. Miyazaki, Y. Wada, K. Okuno, et al., “An Exosome-Based Liquid Biopsy Signature for Pre-Operative Identification of Lymph Node Metastasis in Patients With Pathological High-Risk T1 Colorectal Cancer,” Molecular cancer 22, no. 1 (2023): 2.

[176]

S. A. Cieslik, A. G. Zafra, C. Driemel, et al., “Phenotypic Diversity of Ctcs and Tdevs in Liquid Biopsies of Tumour-Draining Veins Is Linked to Poor Prognosis in Colorectal Cancer,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 9.

[177]

S. Z. Eslami, L. E. Cortés-Hernández, L. Sinoquet, et al., “Circulating Tumour Cells and Pd-L1-Positive Small Extracellular Vesicles: The Liquid Biopsy Combination for Prognostic Information in Patients With Metastatic Non-Small Cell Lung Cancer,” British Journal of Cancer 130, no. 1 (2024): 63–72.

[178]

I. Casanova-Salas, D. Aguilar, S. Cordoba-Terreros, et al., “Circulating Tumor Extracellular Vesicles to Monitor Metastatic Prostate Cancer Genomics and Transcriptomic Evolution,” Cancer Cell 42, no. 7 (2024): 1301–1312.e7.

[179]

N. Schöne, M. Kemper, K. Menck, et al., “Pd-L1 on Large Extracellular Vesicles Is a Predictive Biomarker for Therapy Response in Tissue Pd-L1-Low and -Negative Patients With Non-Small Cell Lung Cancer,” Journal of Extracellular Vesicles 13, no. 3 (2024): e12418.

[180]

K. B. Shanmugasundaram, E. Ahmed, X. Miao, et al., “A Mesoporous Gold Sensor Unveils Phospho Pd-L1 in Extracellular Vesicles as a Proxy for Pd-L1 Expression in Lung Cancer Tissue,” ACS Sens 9, no. 6 (2024): 3009–3016.

[181]

Z. L. Hu, Z. Q. Li, Y. Wang, et al., “Extracellular Vesicles Derived Ebv Tegument Protein Brrf2 Suppresses Cgas Phase Separation to Promote Anti-Viral Innate Immune Evasion,” Nature Communications 16, no. 1 (2025): 9015.

[182]

Y. Ju, J. Watson, J. J. Wang, et al., “B7-H3-Liquid Biopsy for the Characterization and Monitoring of the Dynamic Biology of Prostate Cancer,” Drug Resistance Updates 79 (2025): 101207.

[183]

C. G. Liu, J. Chen, R. M. W. Goh, et al., “The Role of Tumor-Derived Extracellular Vesicles Containing Noncoding Rnas in Mediating Immune Cell Function and Its Implications From Bench to Bedside,” Pharmacological Research 191 (2023): 106756.

[184]

C. Pilotto Heming and V. Aran, “The Potential of Circulating Cell-Free RNA in CNS Tumor Diagnosis and Monitoring: A Liquid Biopsy Approach,” Critical Reviews in Oncology/Hematology 204 (2024): 104504.

[185]

S. Srinivasan, A. Yeri, P. S. Cheah, et al., “Small Rna Sequencing Across Diverse Biofluids Identifies Optimal Methods for Exrna Isolation,” Cell 177, no. 2 (2019): 446–462.e16.

[186]

M. H. Larson, W. Pan, H. J. Kim, et al., “A Comprehensive Characterization of the Cell-Free Transcriptome Reveals Tissue- and Subtype-Specific Biomarkers for Cancer Detection,” Nature Communications 12, no. 1 (2021): 2357.

[187]

L. Cabús, J. Lagarde, J. Curado, et al., “Current Challenges and Best Practices for Cell-Free Long Rna Biomarker Discovery,” Biomarker Research 10, no. 1 (2022): 62.

[188]

S. Xing, Y. Zhu, Y. You, et al., “Cell-Free Rna for the Liquid Biopsy of Gastrointestinal Cancer,” Wiley Interdiscip Rev RNA 14, no. 5 (2023): e1791.

[189]

Y. Li, F. Quan, Y. Wu, et al., “Quantitative Analysis of Cell-Free Rna at Attomolar Level Using Crispr/Cas Digital Imaging Platform,” Analytical Chemistry 96, no. 43 (2024): 17362–17369.

[190]

S. Zhou, H. Sun, J. Dong, et al., “Highly Sensitive and Facile Microrna Detection Based on Target Triggered Exponential Rolling-Circle Amplification Coupling With Crispr/Cas12a,” Analytica Chimica Acta 1265 (2023): 341278.

[191]

H. Yan, Y. Wen, Z. Tian, et al., “A One-Pot Isothermal Cas12-Based Assay for the Sensitive Detection of Micrornas,” Nat Biomed Eng 7, no. 12 (2023): 1583–1601.

[192]

M. Broto, M. M. Kaminski, C. Adrianus, et al., “Nanozyme-Catalysed Crispr Assay for Preamplification-Free Detection of Non-Coding Rnas,” Nature Nanotechnology 17, no. 10 (2022): 1120–1126.

[193]

D. Chen, Y. Wang, Y. Wei, et al., “Size-Coded Hydrogel Microbeads for Extraction-Free Serum Multi-Mirnas Quantifications With Machine-Learning-Aided Lung Cancer Subtypes Classification,” Nano Letters 25, no. 1 (2025): 453–460.

[194]

J. Wang, J. Huang, Y. Hu, et al., “Terminal Modifications Independent Cell-Free Rna Sequencing Enables Sensitive Early Cancer Detection and Classification,” Nature Communications 15, no. 1 (2024): 156.

[195]

R. Stitz, F. Stoiber, R. Silye, et al., “Clinical Implementation of a Noninvasive, Multi-Analyte Droplet Digital Pcr Test to Screen for Androgen Receptor Alterations,” The Journal of Molecular Diagnostics 26, no. 6 (2024): 467–478.

[196]

L. J. Albrecht, A. Höwner, K. Griewank, et al., “Circulating Cell-Free Messenger RNA Enables Non-Invasive Pan-Tumour Monitoring of Melanoma Therapy Independent of the Mutational Genotype,” Clinical and translational medicine 12, no. 11 (2022): e1090.

[197]

R. E. Reggiardo, S. V. Maroli, V. Peddu, et al., “Profiling of Repetitive Rna Sequences in the Blood Plasma of Patients With Cancer,” Nat Biomed Eng 7, no. 12 (2023): 1627–1635.

[198]

M. Metzenmacher, B. Hegedüs, J. Forster, et al., “The Clinical Utility of Cfrna for Disease Detection and Surveillance: A Proof of Concept Study in Non-Small Cell Lung Cancer,” Thorac Cancer 13, no. 15 (2022): 2180–2191.

[199]

E. J. Northrop-Albrecht, C. W. Wu, C. K. Berger, et al., “An Investigation of Plasma Cell-Free Rna for the Detection of Colorectal Cancer: From Transcriptome Marker Selection to Targeted Validation,” PLoS ONE 19, no. 8 (2024): e0308711.

[200]

C. W. Ju, R. Lyu, H. Li, et al., “Modifications of Microbiome-Derived Cell-Free Rna in Plasma Discriminates Colorectal Cancer Samples,” Nature Biotechnology (2025).

[201]

J. Miyoshi, A. Mannucci, M. Scarpa, et al., “Liquid Biopsy to Identify Barrett's Oesophagus, Dysplasia and Oesophageal Adenocarcinoma: The Emerald Multicentre Study,” Gut 74, no. 2 (2025): 169–181.

[202]

A. Safrastyan, C. H. Zu Siederdissen, and D. Wollny, “Decoding Cell-Type Contributions to the Cfrna Transcriptomic Landscape of Liver Cancer,” Human Genomics 17, no. 1 (2023): 90.

[203]

A. Montgomery, G. C. Tsiatsianis, I. Mouratidis, et al., “Utilizing Nullomers in Cell-Free Rna for Early Cancer Detection,” Cancer Gene Therapy 31, no. 6 (2024): 861–870.

[204]

M. Chaddha, H. Rai, R. Gupta, et al., “Integrated Analysis of Circulating Cell Free Nucleic Acids for Cancer Genotyping and Immune Phenotyping of Tumor Microenvironment,” Frontiers in Genetics 14 (2023): 1138625.

[205]

R. Mazzeo, J. Sears, L. Palmero, et al., “Liquid Biopsy in Triple-Negative Breast Cancer: Unlocking the Potential of Precision Oncology,” ESMO Open 9, no. 10 (2024): 103700.

[206]

M. Fukada, N. Matsuhashi, T. Takahashi, et al., “Postoperative Changes in Plasma Mir21-5p as a Novel Biomarker for Colorectal Cancer Recurrence: A Prospective Study,” Cancer Science 112, no. 10 (2021): 4270–4280.

[207]

I. M. Modlin, M. Kidd, I. A. Drozdov, et al., “Development of a Multigenomic Liquid Biopsy (Prostest) for Prostate Cancer in Whole Blood,” Prostate 84, no. 9 (2024): 850–865.

[208]

S. Torresan, M. de Scordilli, M. Bortolot, et al., “Liquid Biopsy in Colorectal Cancer: Onward and Upward,” Critical Reviews in Oncology/Hematology 194 (2024): 104242.

[209]

D. Badr, M. A. Fouad, M. Hussein, et al., “Rebound Increase in Microrna Levels at the End of 5-Fu-Based Therapy in Colorectal Cancer Patients,” Scientific Reports 13, no. 1 (2023): 14237.

[210]

A. Giménez-Capitán, E. Sánchez-Herrero, L. Robado de Lope, et al., “Detecting Alk, Ros1, and Ret Fusions and the MetΔex14 Splicing Variant in Liquid Biopsies of Non-Small-Cell Lung Cancer Patients Using Rna-Based Techniques,” Mol Oncol 17, no. 9 (2023): 1884–1897.

[211]

C. Badowski, B. He, and L. X. Garmire, “Blood-Derived Lncrnas as Biomarkers for Cancer Diagnosis: The Good, the Bad and the Beauty,” NPJ Precis Oncol 6, no. 1 (2022): 40.

[212]

S. Hedayat, L. Cascione, D. Cunningham, et al., “Circulating Microrna Analysis in a Prospective Co-Clinical Trial Identifies Mir652-3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer,” Clinical Cancer Research 30, no. 10 (2024): 2140–2159.

[213]

Y. Zhang and Z. Zhang, “The History and Advances in Cancer Immunotherapy: Understanding the Characteristics of Tumor-Infiltrating Immune Cells and Their Therapeutic Implications,” Cellular & Molecular Immunology 17, no. 8 (2020): 807–821.

[214]

Q. Zhang, M. Ye, C. Lin, et al., “Mass Cytometry-Based Peripheral Blood Analysis as a Novel Tool for Early Detection of Solid Tumours: A Multicentre Study,” Gut 72, no. 5 (2023): 996–1006.

[215]

W. L. Chin, A. M. Cook, J. Chee, et al., “Coupling of Response Biomarkers Between Tumor and Peripheral Blood in Patients Undergoing Chemoimmunotherapy,” Cell Reports Medicine 6, no. 1 (2025): 101882.

[216]

T. Zhang, A. R. Warden, Y. Li, et al., “Progress and Applications of Mass Cytometry in Sketching Immune Landscapes,” Clinical and translational medicine 10, no. 6 (2020): e206.

[217]

D. Dyikanov, A. Zaitsev, T. Vasileva, et al., “Comprehensive Peripheral Blood Immunoprofiling Reveals Five Immunotypes With Immunotherapy Response Characteristics in Patients With Cancer,” Cancer Cell 42, no. 5 (2024): 759–779.e12.

[218]

T. Wang, P. Li, Q. Qi, et al., “A Multiplex Blood-Based Assay Targeting DNA Methylation in Pbmcs Enables Early Detection of Breast Cancer,” Nature Communications 14, no. 1 (2023): 4724.

[219]

K. Challa, D. Paysan, D. Leiser, et al., “Imaging and Ai Based Chromatin Biomarkers for Diagnosis and Therapy Evaluation From Liquid Biopsies,” NPJ Precis Oncol 7, no. 1 (2023): 135.

[220]

M. J. Stagno, A. Schmidt, J. Bochem, et al., “Epitope Detection in Monocytes (Edim) for Liquid Biopsy Including Identification of Gd2 in Childhood Neuroblastoma-a Pilot Study,” British Journal of Cancer 127, no. 7 (2022): 1324–1331.

[221]

S. Shai, F. Patolsky, H. Drori, et al., “A Novel, Accurate, and Non-Invasive Liquid Biopsy Test to Measure Cellular Immune Responses as a Tool to Diagnose Early-Stage Lung Cancer: A Clinical Trials Study,” Respiratory Research 24, no. 1 (2023): 52.

[222]

K. Charoenkwan, N. Apaijai, S. Sriwichaiin, et al., “Alterations in Mitochondria Isolated From Peripheral Blood Mononuclear Cells and Tumors of Patients With Epithelial Ovarian Cancers,” Scientific Reports 14, no. 1 (2024): 15.

[223]

A. Martinez-Usatorre, L. Ciarloni, P. Angelino, et al., “Human Blood Cell Transcriptomics Unveils Dynamic Systemic Immune Modulation along Colorectal Cancer Progression,” Journal for ImmunoTherapy of Cancer 12, no. 11 (2024): e009888.

[224]

M. Basu, K. Wang, E. Ruppin, et al., “Predicting Tissue-Specific Gene Expression From Whole Blood Transcriptome,” Science Advances 7, no. 14 (2021): eabd6991.

[225]

Y. Cao, T. Chang, F. Schischlik, et al., “Inferring Characteristics of the Tumor Immune Microenvironment of Patients With Hnscc From Single-Cell Transcriptomics of Peripheral Blood,” Cancer Research Communications 4, no. 9 (2024): 2335–2348.

[226]

L. L. Miao, J. W. Wang, H. H. Liu, et al., “Hypomethylation of Glycine Dehydrogenase Promoter in Peripheral Blood Mononuclear Cells Is a New Diagnostic Marker of Hepatitis B Virus-Associated Hepatocellular Carcinoma,” Hepatobiliary & Pancreatic Diseases International 23, no. 1 (2024): 35–42.

[227]

F. Mao, C. Yang, W. Luo, et al., “Peripheral Blood Lymphocyte Subsets Are Associated With the Clinical Outcomes of Prostate Cancer Patients,” International Immunopharmacology 113, no. Pt A (2022): 109287.

[228]

X. Xu, F. Wei, L. Xiao, et al., “High Proportion of Circulating Cd8 + Cd28- Senescent T Cells Is an Independent Predictor of Distant Metastasis in Nasopharyngeal Canrcinoma After Radiotherapy,” Journal of translational medicine 21, no. 1 (2023): 64.

[229]

X. Liu, X. Cheng, F. Xie, et al., “Persistence of Peripheral Cd8 + Cd28- T Cells Indicates a Favourable Outcome and Tumour Immunity in First-Line Her2-Positive Metastatic Breast Cancer,” British Journal of Cancer 130, no. 10 (2024): 1599–1608.

[230]

L. A. Salas, Z. Zhang, D. C. Koestler, et al., “Enhanced Cell Deconvolution of Peripheral Blood Using DNA Methylation for High-Resolution Immune Profiling,” Nature Communications 13, no. 1 (2022): 761.

[231]

N. Loyfer, J. Magenheim, A. Peretz, et al., “A DNA Methylation Atlas of Normal Human Cell Types,” Nature 613, no. 7943 (2023): 355–364.

[232]

Q. Luo, V. B. Dwaraka, Q. Chen, et al., “A Meta-Analysis of Immune-Cell Fractions at High Resolution Reveals Novel Associations With Common Phenotypes and Health Outcomes,” Genome Medicine 15, no. 1 (2023): 59.

[233]

J. Q. Chen, L. A. Salas, J. K. Wiencke, et al., “Genome-Scale Methylation Analysis Identifies Immune Profiles and Age Acceleration Associations With Bladder Cancer Outcomes,” Cancer Epidemiology and Prevention Biomarkers 32, no. 10 (2023): 1328–1337.

[234]

V. Singh, S. Nandi, A. Ghosh, et al., “Epigenetic Reprogramming of T Cells: Unlocking New Avenues for Cancer Immunotherapy,” Cancer and Metastasis Reviews 43, no. 1 (2024): 175–195.

[235]

G. Zhang, A. Liu, Y. Yang, et al., “Clinical Predictive Value of Naïve and Memory T Cells in Advanced Nsclc,” Frontiers in Immunology 13 (2022): 996348.

[236]

R. Ferrara, M. Naigeon, E. Auclin, et al., “Circulating T-Cell Immunosenescence in Patients With Advanced Non-Small Cell Lung Cancer Treated With Single-Agent Pd-1/Pd-L1 Inhibitors or Platinum-Based Chemotherapy,” Clinical Cancer Research 27, no. 2 (2021): 492–503.

[237]

B. Duchemann, M. Naigeon, E. Auclin, et al., “Cd8+Pd-1+ to Cd4+Pd-1+ Ratio (Perls) Is Associated With Prognosis of Patients With Advanced Nsclc Treated With Pd-(L)1 Blockers,” Journal for Immunotherapy of Cancer 10, no. 2 (2022): e004012.

[238]

A. M. Luoma, S. Suo, Y. Wang, et al., “Tissue-Resident Memory and Circulating T Cells Are Early Responders to Pre-Surgical Cancer Immunotherapy,” Cell 185, no. 16 (2022): 2918–2935.e29.

[239]

L. Xia, H. Wang, M. Sun, et al., “Peripheral Cd4(+) T Cell Signatures in Predicting the Responses to Anti-Pd-1/Pd-L1 Monotherapy for Chinese Advanced Non-Small Cell Lung Cancer,” Science China Life Sciences 64, no. 10 (2021): 1590–1601.

[240]

H. Tada, H. Takahashi, K. Yamada, et al., “Dynamic Alterations of Circulating T Lymphocytes and the Clinical Response in Patients With Head and Neck Squamous Cell Carcinoma Treated With Nivolumab,” Cancer Immunology, Immunotherapy 71, no. 4 (2022): 851–863.

[241]

C. Olingy, A. Alimadadi, D. J. Araujo, et al., “Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-Pd-1 Immunotherapy Against Non-Small Cell Lung Cancer,” Frontiers in immunology 13 (2022): 842653.

[242]

N. Okiyama and R. Tanaka, “Immune-Related Adverse Events in Various Organs Caused by Immune Checkpoint Inhibitors,” Allergol Int 71, no. 2 (2022): 169–178.

[243]

R. Geng, H. Tang, T. You, et al., “Peripheral Cd8+Cd28+ T Lymphocytes Predict the Efficacy and Safety of Pd-1/Pd-L1 Inhibitors in Cancer Patients,” Frontiers in immunology 14 (2023): 1125876.

[244]

N. Earland, W. Zhang, A. Usmani, et al., “Cd4 T Cells and Toxicity From Immune Checkpoint Blockade,” Immunological Reviews 318, no. 1 (2023): 96–109.

[245]

J. C. Murray, L. Sivapalan, K. Hummelink, et al., “Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal Ctdna and Immune Cell Compartment Tracking in Lung Cancer,” Clinical Cancer Research 30, no. 2 (2024): 389–403.

[246]

R. Ghosh, R. Ahmed, H. Ahmed, et al., “Phosphorylated Proteins From Serum: A Promising Potential Diagnostic Biomarker of Cancer,” International Journal of Molecular Sciences 23, no. 20 (2022): 12359.

[247]

C. Dhar, P. Ramachandran, G. Xu, et al., “Diagnosing and Staging Epithelial Ovarian Cancer by Serum Glycoproteomic Profiling,” British Journal of Cancer 130, no. 10 (2024): 1716–1724.

[248]

H. Hayashi, K. Chamoto, R. Hatae, et al., “Soluble Immune Checkpoint Factors Reflect Exhaustion of Antitumor Immunity and Response to Pd-1 Blockade,” Journal of Clinical Investigation 134, no. 7 (2024): e168318.

[249]

I. Sam, N. Ben Hamouda, M. Alkatrib, et al., “The Cd70-Cd27 Axis in Cancer Immunotherapy: Predictive Biomarker and Therapeutic Target,” Clinical Cancer Research 31, no. 14 (2025): 2872–2881.

[250]

X. Xu, L. Tang, Y. Yu, et al., “Cooperative Amplification of Prussian Blue as a Signal Indicator and Functionalized Metal-Organic Framework-Based Electrochemical Biosensor for an Ultrasensitive He4 Assay,” Biosensors & Bioelectronics 262 (2024): 116541.

[251]

Z. Zhong, L. Ding, Z. Man, et al., “Versatile Metal-Organic Framework Incorporating Ag(2)S for Constructing a Photoelectrochemical Immunosensor for Two Breast Cancer Markers,” Analytical Chemistry 96, no. 21 (2024): 8837–8843.

[252]

M. Yang, L. Wang, C. Xie, et al., “A Disposable Ultrasensitive Immunosensor Based on Mxene/Nh(2)-Cnt Modified Screen-Printed Electrode for the Detection of Ovarian Cancer Antigen Ca125,” Talanta 281 (2025): 126893.

[253]

R. Liu, H. Song, H. Wu, et al., “Sub-Femtomolar Vertical Graphene Field Effect Immunosensor for Detection of Lung Tumor Markers,” Talanta 278 (2024): 126498.

[254]

P. Johnson, Q. Zhou, D. Y. Dao, et al., “Circulating Biomarkers in the Diagnosis and Management of Hepatocellular Carcinoma,” Nature reviews Gastroenterology & hepatology 19, no. 10 (2022): 670–681.

[255]

M. Ota, K. Komeda, H. Iida, et al., “The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients With Hepatocellular Carcinoma,” Annals of Surgical Oncology 30, no. 5 (2023): 2807–2815.

[256]

Z. Ding, N. Wang, N. Ji, et al., “Proteomics Technologies for Cancer Liquid Biopsies,” Molecular Cancer 21, no. 1 (2022): 53.

[257]

M. Cui, C. Cheng, and L. Zhang, “High-Throughput Proteomics: A Methodological Mini-Review,” Laboratory Investigation; a Journal of Technical Methods and Pathology 102, no. 11 (2022): 1170–1181.

[258]

B. Gurbuz, N. Guldiken, P. Reuken, et al., “Biomarkers of Hepatocellular Synthesis in Patients With Decompensated Cirrhosis,” Hepatology International 17, no. 3 (2023): 698–708.

[259]

W. Kajornsrichon, J. Chaisaingmongkol, Y. Pomyen, et al., “Identification of Autoantibodies as Potential Non-Invasive Biomarkers for Intrahepatic Cholangiocarcinoma,” Scientific Reports 14, no. 1 (2024): 20012.

[260]

T. Li, G. Sun, H. Ye, et al., “Esccpred: A Machine Learning Model for Diagnostic Prediction of Early Esophageal Squamous Cell Carcinoma Using Autoantibody Profiles,” British Journal of Cancer 131, no. 5 (2024): 883–894.

[261]

B. Dong, H. Zhang, Y. Duan, et al., “Development of a Machine Learning-Based Model to Predict Prognosis of Alpha-Fetoprotein-Positive Hepatocellular Carcinoma,” Journal of translational medicine 22, no. 1 (2024): 455.

[262]

A. Hu, L. Zhang, Z. Wang, et al., “Cancer Serum Atlas-Supported Precise Pan-Targeted Proteomics Enable Multicancer Detection,” Analytical Chemistry 95, no. 2 (2023): 862–871.

[263]

R. C. Joshi, P. Srivastava, R. Mishra, et al., “Biomarker Profiling and Integrating Heterogeneous Models for Enhanced Multi-Grade Breast Cancer Prognostication,” Computer Methods and Programs in Biomedicine 255 (2024): 108349.

[264]

M. Chen, J. Ma, X. Xie, et al., “Serum Itih5 as a Novel Diagnostic Biomarker in Cholangiocarcinoma,” Cancer Science 115, no. 5 (2024): 1665–1679.

[265]

J. Sun, J. Zhao, F. Jiang, et al., “Identification of Novel Protein Biomarkers and Drug Targets for Colorectal Cancer by Integrating Human Plasma Proteome With Genome,” Genome Medicine 15, no. 1 (2023): 75.

[266]

M. A. Sharafeldin, R. A. Suef, A. A. Mousa, et al., “Serum Interleukin-10 and Alpha-Fetoprotein: A Combined Diagnostic Approach for Hepatocellular Carcinoma in Egyptians With Hcv,” Pathology, Research and Practice 258 (2024): 155327.

[267]

L. Huang, X. Deng, R. Z. Fan, et al., “Coagulation and Fibrinolytic Markers Offer Utility When Distinguishing Between Benign and Malignant Gallbladder Tumors: A Cross-Sectional Study,” Clinica Chimica Acta 560 (2024): 119751.

[268]

S. Byeon, M. J. McKay, M. P. Molloy, et al., “Novel Serum Protein Biomarker Panel for Early Diagnosis of Pancreatic Cancer,” International Journal of Cancer 155, no. 2 (2024): 365–371.

[269]

Y. Cai, K. Xie, M. N. Adeeb Alhmoud, et al., “Effect of Pivka-Ii and Afp Secretion Status on Early Recurrence of Hepatocellular Carcinoma After Open and Laparoscopic Surgery,” Cancer medicine 12, no. 17 (2023): 17866–17877.

[270]

X. Ye, C. Li, X. Zu, et al., “A Large-Scale Multicenter Study Validates Aldo-Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma,” Hepatology 69, no. 6 (2019): 2489–2501.

[271]

C. Xie, X. Ye, L. Zeng, et al., “Serum Akr1b10 as an Indicator of Unfavorable Survival of Hepatocellular Carcinoma,” Journal of Gastroenterology 58, no. 10 (2023): 1030–1042.

[272]

Y. Toda, K. Ogura, S. Iwata, et al., “The Diagnostic and Prognostic Value of Tartrate-Resistant Acid Phosphatase Isoform 5b for Giant Cell Tumor of Bone,” International Journal of Clinical Oncology 29, no. 9 (2024): 1391–1397.

[273]

C. An, R. Wei, W. Yao, et al., “Association of Serum Afp Trajectories and Hepatocellular Carcinoma Outcomes After Hepatic Arterial Infusion Chemotherapy: A Longitudinal, Multicenter Study,” Cancer medicine 13, no. 11 (2024): e7319.

[274]

F. B. Gunnarsdottir, P. O. Bendahl, A. Johansson, et al., “Serum Immuno-Oncology Markers Carry Independent Prognostic Information in Patients With Newly Diagnosed Metastatic Breast Cancer, From a Prospective Observational Study,” Breast Cancer Research 25, no. 1 (2023): 29.

[275]

N. Prueksaritanond, S. Angsathapon, and P. Insin, “The Utility of Preoperative Serum Ca125 Combined With He4 to Predict Lymph Node Metastasis in Endometrial Cancer,” Gynecologic and Obstetric Investigation 88, no. 1 (2023): 53–60.

[276]

N. Guo, G. Minas, S. A. Synowsky, et al., “Identification of Plasma Proteins Associated With Oesophageal Cancer Chemotherapeutic Treatment Outcomes Using Swath-Ms,” Journal of Proteomics 266 (2022): 104684.

[277]

P. Mondelo-Macía, J. García-González, L. León-Mateos, et al., “Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer,” Molecular & Cellular Proteomics 23, no. 10 (2024): 100834.

[278]

A. Csizmarik, N. Nagy, D. Keresztes, et al., “Comparative Proteome and Serum Analysis Identified Fscn1 as a Marker of Abiraterone Resistance in Castration-Resistant Prostate Cancer,” Prostate Cancer and Prostatic Diseases 27, no. 3 (2024): 451–456.

[279]

A. Csizmarik, D. Keresztes, N. Nagy, et al., “Proteome Profiling of Enzalutamide-Resistant Cell Lines and Serum Analysis Identified Alcam as Marker of Resistance in Castration-Resistant Prostate Cancer,” International Journal of Cancer 151, no. 8 (2022): 1405–1419.

[280]

I. Pourmir, N. Benhamouda, T. Tran, et al., “Soluble Tim-3, Likely Produced by Myeloid Cells, Predicts Resistance to Immune Checkpoint Inhibitors in Metastatic Clear Cell Renal Cell Carcinoma,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 54.

[281]

C. Chen, F. Zhao, J. Peng, et al., “Soluble Tim-3 Serves as a Tumor Prognostic Marker and Therapeutic Target for Cd8(+) T Cell Exhaustion and Anti-Pd-1 Resistance,” Cell Reports Medicine 5, no. 8 (2024): 101686.

[282]

Y. Li, B. Wang, W. Yang, et al., “Longitudinal Plasma Proteome Profiling Reveals the Diversity of Biomarkers for Diagnosis and Cetuximab Therapy Response of Colorectal Cancer,” Nature Communications 15, no. 1 (2024): 980.

[283]

Q. Gao, Y. P. Lin, B. S. Li, et al., “Unintrusive Multi-Cancer Detection by Circulating Cell-Free DNA Methylation Sequencing (Thunder): Development and Independent Validation Studies,” Annals of Oncology 34, no. 5 (2023): 486–495.

[284]

M. C. Nesselbush, B. A. Luca, Y. J. Jeon, et al., “An Ultrasensitive Method for Detection of Cell-Free Rna,” Nature 641, no. 8063 (2025): 759–768.

[285]

P. T. B. Ho, I. M. Clark, and L. T. T. Le, “Microrna-Based Diagnosis and Therapy,” International Journal of Molecular Sciences 23, no. 13 (2022): 7167.

[286]

C. Alix-Panabières and K. Pantel, “Advances in Liquid Biopsy: From Exploration to Practical Application,” Cancer Cell 43, no. 2 (2025): 161–165.

[287]

T. R. Lee, J. M. Ahn, J. Lee, et al., “Integrating Plasma Cell-Free DNA Fragment End Motif and Size With Genomic Features Enables Lung Cancer Detection,” Cancer Research 85, no. 9 (2025): 1696–1707.

[288]

Y. Tao, S. Xing, S. Zuo, et al., “Cell-Free Multi-Omics Analysis Reveals Potential Biomarkers in Gastrointestinal Cancer Patients' Blood,” Cell Reports Medicine 4, no. 11 (2023): 101281.

[289]

A. Bortolini Silveira, F. C. Bidard, M. L. Tanguy, et al., “Multimodal Liquid Biopsy for Early Monitoring and Outcome Prediction of Chemotherapy in Metastatic Breast Cancer,” NPJ Breast Cancer 7, no. 1 (2021): 115.

[290]

L. Gerratana, A. A. Davis, L. Foffano, et al., “Integrating Machine Learning-Predicted Circulating Tumor Cells (Ctcs) and Circulating Tumor DNA (Ctdna) in Metastatic Breast Cancer: A Proof of Principle Study on Endocrine Resistance Profiling,” Cancer Letters 609 (2025): 217325.

[291]

J. R. Andrews, Y. Kim, E. Horjeti, et al., “Psma+ Extracellular Vesicles Are a Biomarker for Sabr in Oligorecurrent Prostate Cancer: Analysis From the Stomp-Like and Oriole Trial Cohorts,” Clinical Cancer Research 31, no. 6 (2025): 1142–1149.

[292]

L. Paschold, A. Stein, B. Thiele, et al., “First-Line Treatment of Unresectable or Metastatic Her2 Positive Esophagogastric Adenocarcinoma: Liquid Biomarker Analysis of the Phase 2 Intega Trial,” Journal for ImmunoTherapy of Cancer 11, no. 6 (2023): e006678.

[293]

F. Wang, C. Wang, S. Chen, et al., “Identification of Blood-Derived Exosomal Tumor Rna Signatures as Noninvasive Diagnostic Biomarkers for Multi-Cancer: A Multi-Phase, Multi-Center Study,” Molecular cancer 24, no. 1 (2025): 60.

[294]

C. Kurzeder, B. D. Nguyen-Sträuli, I. Krol, et al., “Digoxin for Reduction of Circulating Tumor Cell Cluster Size in Metastatic Breast Cancer: A Proof-of-Concept Trial,” Nature Medicine 31, no. 4 (2025): 1120–1124.

[295]

A. A. Javed, D. Ding, A. Hasanain, et al., “Persistent Circulating Tumor Cells at 1 Year After Oncologic Resection Predict Late Recurrence in Pancreatic Cancer,” Annals of Surgery 277, no. 6 (2023): 859–865.

[296]

I. van 't Erve, J. E. Medina, A. Leal, et al., “Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells,” Clinical Cancer Research 29, no. 5 (2023): 899–909.

[297]

R. Zhang, Y. Nie, X. Chen, et al., “A Multicenter Prospective Clinical Trial Reveals Cell-Free DNA Methylation Markers for Early Esophageal Cancer,” Journal of Clinical Investigation 135, no. 8 (2025): e186816.

[298]

L. Han, Y. Song, L. Tong, et al., “Extracellular Vesicle Protein Panel Enables Early Lung Cancer Detection in a Large Clinical Cohort,” Journal of Extracellular Vesicles 14, no. 8 (2025): e70129.

[299]

A. Goldkorn, C. Tangen, M. Plets, et al., “Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer,” JAMA Network Open 7, no. 10 (2024): e2437871.

[300]

M. M. Syeda, G. V. Long, J. Garrett, et al., “Clinical Validation of Droplet Digital Pcr Assays in Detecting Braf(V600)-Mutant Circulating Tumour DNA as a Prognostic Biomarker in Patients With Resected Stage Iii Melanoma Receiving Adjuvant Therapy (Combi-Ad): A Biomarker Analysis From a Double-Blind, Randomised Phase 3 Trial,” The Lancet Oncology 26, no. 5 (2025): 641–653.

[301]

T. Fehm, V. Mueller, M. Banys-Paluchowski, et al., “Efficacy of Lapatinib in Patients With Her2-Negative Metastatic Breast Cancer and Her2-Positive Circulating Tumor Cells-the Detect Iii Clinical Trial,” Clinical Chemistry 70, no. 1 (2024): 307–318.

[302]

L. Gerratana, C. Reduzzi, Y. Ren, et al., “Circulating Tumor Cell Dynamics After Cdk4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis From the Pace Phase Ii Study,” Clinical Cancer Research 31, no. 21 (2025): 4510–4517.

[303]

S. Jun, N. A. Shukla, G. Durm, et al., “Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage Iii Nsclc,” Journal of thoracic oncology 19, no. 10 (2024): 1427–1437.

[304]

C. J. Sweeney, R. Petry, C. Xu, et al., “Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to Psa in Metastatic Castration-Resistant Prostate Cancer,” Clinical Cancer Research 30, no. 18 (2024): 4115–4122.

[305]

J. Zhong, K. Fei, L. Wu, et al., “Toripalimab Plus Chemotherapy for First Line Treatment of Advanced Non-Small Cell Lung Cancer (Choice-01): Final Os and Biomarker Exploration of a Randomized, Double-Blind, Phase 3 Trial,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 369.

[306]

N. Gaynor, A. Blanco, S. F. Madden, et al., “Alterations in Immune Cell Phenotype and Cytotoxic Capacity in Her2+ Breast Cancer Patients Receiving Her2-Targeted Neo-Adjuvant Therapy,” British Journal of Cancer 129, no. 6 (2023): 1022–1031.

[307]

S. W. Huang, W. Jiang, S. Xu, et al., “Systemic Longitudinal Immune Profiling Identifies Proliferating Treg Cells as Predictors of Immunotherapy Benefit: Biomarker Analysis From the Phase 3 Continuum and Dipper Trials,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 285.

[308]

D. Y. Yuan, M. L. McKeague, V. K. Raghu, et al., “Immune Cell Transcriptional Profiles From Pre-Vaccination Peripheral Blood Predict Immune Response to Preventative Muc1 Cancer Vaccine,” European Journal of Cancer 228 (2025): 115685.

[309]

Y. Guo, S. Luo, S. Liu, et al., “Bimodal in Situ Analyzer for Circular Rna in Extracellular Vesicles Combined With Machine Learning for Accurate Gastric Cancer Detection,” Advanced Science (Weinh) 12, no. 15 (2025): e2409202.

[310]

H. Ding, M. Yuan, Y. Yang, et al., “Identifying Key Circulating Tumor DNA Parameters for Predicting Clinical Outcomes in Metastatic Non-Squamous Non-Small Cell Lung Cancer After First-Line Chemoimmunotherapy,” Nature Communications 15, no. 1 (2024): 6862.

[311]

A. Sala, J. M. Cameron, P. M. Brennan, et al., “Global Serum Profiling: An Opportunity for Earlier Cancer Detection,” Journal of Experimental & Clinical Cancer Research 42, no. 1 (2023): 207.

[312]

C. Ren, X. Chen, X. Hao, et al., “Integrated Machine Learning Algorithms Reveal a Bone Metastasis-Related Signature of Circulating Tumor Cells in Prostate Cancer,” Scientific Data 11, no. 1 (2024): 701.

[313]

Y. Jia, Y. Li, X. Bai, et al., “Raman Spectroscopy and Exosome-Based Machine Learning Predicts the Efficacy of Neoadjuvant Therapy for Her2-Positive Breast Cancer,” Analytical Chemistry 97, no. 2 (2025): 1374–1385.

[314]

A. J. Widman, M. Shah, A. Frydendahl, et al., “Ultrasensitive Plasma-Based Monitoring of Tumor Burden Using Machine-Learning-Guided Signal Enrichment,” Nature Medicine 30, no. 6 (2024): 1655–1666.

[315]

G. Zhu, C. R. Rahman, V. Getty, et al., “A Deep-Learning Model for Quantifying Circulating Tumour DNA From the Density Distribution of DNA-Fragment Lengths,” Nat Biomed Eng 9, no. 3 (2025): 307–319.

[316]

X. W. Zhang, G. X. Qi, M. X. Liu, et al., “Deep Learning Promotes Profiling of Multiple Mirnas in Single Extracellular Vesicles for Cancer Diagnosis,” ACS Sens 9, no. 3 (2024): 1555–1564.

[317]

X. Diao, X. Li, S. Hou, et al., “Machine Learning-Based Label-Free Sers Profiling of Exosomes for Accurate Fuzzy Diagnosis of Cancer and Dynamic Monitoring of Drug Therapeutic Processes,” Analytical Chemistry 95, no. 19 (2023): 7552–7559.

[318]

P. Bao, T. Wang, X. Liu, et al., “Peak Analysis of Cell-Free Rna Finds Recurrently Protected Narrow Regions With Clinical Potential,” Genome biology 26, no. 1 (2025): 119.

[319]

R. Zenhausern, A. S. Day, B. Safavinia, et al., “Natural Killer Cell Detection, Quantification, and Subpopulation Identification on Paper Microfluidic Cell Chromatography Using Smartphone-Based Machine Learning Classification,” Biosensors & Bioelectronics 200 (2022): 113916.

[320]

J. Liu, D. Hu, Y. Lin, et al., “Early Detection of Uterine Corpus Endometrial Carcinoma Utilizing Plasma Cfdna Fragmentomics,” BMC Medicine [Electronic Resource] 22, no. 1 (2024): 310.

[321]

Y. Cao, N. Wang, X. Wu, et al., “Multidimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer,” Cancer Research 84, no. 19 (2024): 3286–3295.

[322]

S. Wang, F. Meng, M. Li, et al., “Multidimensional Cell-Free DNA Fragmentomic Assay for Detection of Early-Stage Lung Cancer,” American Journal of Respiratory and Critical Care Medicine 207, no. 9 (2023): 1203–1213.

[323]

J. Liu, L. Dai, Q. Wang, et al., “Multimodal Analysis of Cfdna Methylomes for Early Detecting Esophageal Squamous Cell Carcinoma and Precancerous Lesions,” Nature Communications 15, no. 1 (2024): 3700.

[324]

A. Lapitz, M. Azkargorta, P. Milkiewicz, et al., “Liquid Biopsy-Based Protein Biomarkers for Risk Prediction, Early Diagnosis, and Prognostication of Cholangiocarcinoma,” Journal of Hepatology 79, no. 1 (2023): 93–108.

[325]

X. Gu, Z. Fan, L. Lu, et al., “Machine Learning-Assisted Washing-Free Detection of Extracellular Vesicles by Target Recycling Amplification Based Fluorescent Aptasensor for Accurate Diagnosis of Gastric Cancer,” Talanta 287 (2025): 127506.

[326]

M. Karimzadeh, A. Momen-Roknabadi, T. B. Cavazos, et al., “Deep Generative Ai Models Analyzing Circulating Orphan Non-Coding Rnas Enable Detection of Early-Stage Lung Cancer,” Nature Communications 15, no. 1 (2024): 10090.

[327]

Y. Cai, M. Luo, W. Yang, et al., “The Deep Learning Framework Icantcr Enables Early Cancer Detection Using the T-Cell Receptor Repertoire in Peripheral Blood,” Cancer Research 84, no. 11 (2024): 1915–1928.

[328]

Y. W. Xu, Y. H. Peng, C. T. Liu, et al., “Machine Learning Technique-Based Four-Autoantibody Test for Early Detection of Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study With a Nested Case-Control Study,” BMC Medicine [Electronic Resource] 23, no. 1 (2025): 235.

[329]

J. Keyl, S. Kasper, M. Wiesweg, et al., “Multimodal Survival Prediction in Advanced Pancreatic Cancer Using Machine Learning,” ESMO Open 7, no. 5 (2022): 100555.

[330]

Z. Liu, I. Georgakopoulos-Soares, N. Ahituv, et al., “Risk Scoring Based on DNA Methylation-Driven Related Degs for Colorectal Cancer Prognosis With Systematic Insights,” Life Sciences 316 (2023): 121413.

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