Multiple myeloma (MM) is an incurable malignancy with heterogeneous clinical manifestations and prognoses. The existing staging systems offer assistance in prognosis determination, yet their accuracy in the real-world context is limited, and numerous crucial parameters have been disregarded. Comprehensive exploration of prognostic value parameters for MM patients in the real world is of paramount significance.
In this study, 812 newly diagnosed MM patients treated with standard first-line therapy at Zhongshan Hospital Fudan University from January 2010 to April 2021 were enrolled, representing one of the largest MM cohorts in China. Among them, 703 patients did not receive transplantation (527 in the training set and 176 in the validation set), and 109 patients underwent transplantation. Forty-three baseline parameters encompassing clinical, laboratory, and pathological features were incorporated. Univariate and multivariate Cox analyses were conducted to screen the most prognostically significant parameters.
The results revealed that ten parameters, including ECOG score, extramedullary lesions, platelet count, reticulocyte count, anion gap, hypercalcemia, complement C3, β2-microglobulin, cytogenetics, and interleukin-2 receptor, were of the greatest prognostic value. These parameters include some integrated into current mainstream staging systems and many previously overlooked. A risk scoring system was developed using these ten parameters, demonstrating relatively high accuracy.
This research comprehensively evaluated the baseline disease characteristics of a wide range of MM patients, validated and identified the clinical significance of various parameters, providing new evidence for accurate prognosis determination of patients.
Laryngeal squamous cell carcinoma (LSCC) ranks among the most commonly diagnosed cancers of head and neck cancers. This study aimed to devise a nomogram capable of predicting cancer-specific survival (CSS) of LSCC patients.
From the Surveillance, Epidemiology, and End Results (SEER) database, 3866 patients with LSCC diagnosed between 2000 and 2020 were selected. These patients were evenly split into a training cohort (n = 1933) and a validation cohort (n = 1933). Univariable and multivariable Cox regression analyses were employed to identify independent prognostic factors for CSS, which were subsequently integrated to develop a nomogram. The nomogram's predictive accuracy and discriminative ability were thoroughly assessed using various metrics. Additionally, a comparative analysis was performed against the tumor-node-metastasis (TNM) staging system.
Eight independent prognostic factors were integrated into the nomogram. Excellent discrimination was exhibited by both the training and validation cohorts, as evidenced by the C-index and calibration curves. In the training group, the area under the curve (AUC) values at 1, 3, and 5 years were 0.728, 0.746, and 0.766, respectively, while in the validation group, they were 0.771, 0.751, and 0.763, respectively. When compared to the traditional TNM staging system, three metrics consistently demonstrated the superior performance of the nomogram.
This study successfully constructed a novel and well-calibrated nomogram, serving as a convenient, practical, and efficient clinical decision-making tool that offers precise prognostic information for patients with LSCC.
Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous tumor. Molecular profiling serves as the foundation for personalized treatment of ICC. Comprehensive molecular testing is needed to identify more patients that are suitable for specific targeted therapies. This consensus is based on clinical data from both domestic and international sources, tailored to the Chinese context, and focuses on key targets for ICC. We present 15 recommendations aimed at guiding the precision detection of ICC.
Driven by recent scientific breakthroughs that underscore the critical role of the immune system in tumor development, strategies targeting the immune system have emerged as a promising avenue for cancer therapy. Therapeutic vaccine strategies represent a dynamic and evolving approach in cancer immunotherapy, offering the potential for more effective and personalized treatment options for patients. This review describes significant advancements in therapeutic vaccine strategies that leverage the immune response to target and eliminate cancer cells. The combination of these vaccines with immune checkpoint inhibitors has shown encouraging clinical outcomes, including improved survival rates and tumor reduction across multiple cancer types. This review also addresses key challenges for cancer vaccines such as overall low immunogenicity and tumor heterogeneity, highlighting the potential of combination therapies to overcome these barriers and enhance treatment efficacy.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with lung cancer, including improving their survival rates. Immune checkpoint inhibitor-associated myocardial infarction is a rare but serious complication of using ICIs. We here present a case of a 70-year-old man who developed ICI-associated myocardial infarction, underwent percutaneous coronary stent implantation, and subsequently received standard oral medication. Chemotherapy was resumed after tumor progression was identified, at which time a review of coronary computed tomography angiography showed no stent stenosis. Strengthening the education and supervision of patients with cancer receiving ICIs and identifying and managing ICI-associated atherosclerosis in a timely manner is therefore necessary.
As the third leading cause of cancer-related mortality worldwide, hepatocellular carcinoma (HCC) constitutes a substantial global health burden. Immunotherapy has transformed HCC management, encompassing immune checkpoint inhibitors, cytokine-based therapies, adoptive cell therapies, and oncolytic viruses. Clinical research is increasingly focused on combination immunotherapy, which offers improved treatment prospects, particularly for patients with unresectable HCC. This review provides a concise overview of the HCC immune microenvironment, emphasizing the role of immune cells in HCC pathogenesis and progression. Additionally, it examines the molecular mechanisms underlying HCC immunotherapy, summarizes relevant clinical trials and their outcomes, discusses key therapeutic agents and combination strategies, and addresses current challenges and future directions in the field.
In this study, a bibliometric analysis was performed to systematically characterize the research landscape of small molecule compounds for lung cancer (LC) treatment and identify emerging trends.
Data were extracted from the Web of Science Core Collection. The bibliometric software tools VOSviewer and CiteSpace were used to analyze publication trends, institutional collaboration networks, author contributions, and keyword co-occurrence patterns. Additionally, the patent portfolios of high-output authors and highly cited researchers were quantified.
Annual publications have exhibited steady growth since 2011, with Asian countries (notably China) dominating output (80% of the top 10 institutions) and the USA leading in citation impact (52.79 average citations/publication). The patent analysis revealed a preponderant focus on drug synthesis methodologies, with high-output authors showing significant patent productivity. The co-occurrence analysis identified shifting research frontiers: early emphasis on epidermal growth factor receptor inhibitors transitioned post-2016 to emerging themes, including molecular docking, cancer metabolism, and migration.
This study highlights the translational emphasis of small molecule research in LC. However, significant geographical disparities exist, with Asian countries dominating publication output and the USA maintaining preeminence in citation impact. Future research should prioritize overcoming acquired resistance, leveraging natural product optimization, drug repurposing, advancing delivery systems, and exploring combination therapies.
Lipid metabolism plays a crucial role in cancer progression, and long non-coding RNAs (lncRNAs) are emerging as key regulators in tumor biology. However, the prognostic and therapeutic implications of lipid metabolism-related lncRNAs in lung adenocarcinoma (LUAD) remain unclear. This study aimed to identify lipid metabolism-associated lncRNAs, construct a prognostic model, and explore their clinical relevance in LUAD.
Transcriptomic and clinical data from LUAD patients were obtained from The Cancer Genome Atlas (TCGA). Co-expression networks, functional enrichment (GO/KEGG), and survival analyses (univariate/multivariate Cox regression, LASSO) were used to identify prognostic lncRNAs. A risk prediction model was developed and validated using tumor mutation burden (TMB), immune microenvironment analysis, and drug sensitivity profiling. Mendelian randomization (MR) and Bayesian weighting were employed to assess causal relationships between lipid metabolism pathways and LUAD.
Three lipid metabolism-related lncRNAs—LINC00862 and AC125807.2 (risk factors) and LINC01447 (protective factor)—were significantly associated with LUAD prognosis. The risk model stratified patients into high- and low-risk groups with distinct sur-vival outcomes (p < 0.001). High-risk patients exhibited elevated TMB and immune dysfunction but greater sensitivity to chemotherapy (e.g., cisplatin, gemcitabine), while low-risk patients showed potential responsiveness to targeted therapies (e.g., PAK1/GSK-3 inhibitors). MR analysis confirmed that normal lipid metabolism pathways (linoleic acid/fatty acid metabolism) reduce LUAD risk (IVW p < 0.05).
This study identifies lipid metabolism-related lncRNAs as novel prognostic biomarkers in LUAD, with implications for risk stratification and personalized therapy. The findings highlight the interplay between lipid metabolism, immune regulation, and therapeutic response, offering a foundation for future clinical validation and targeted interventions.
Chimeric antigen receptor T-cell (CAR T-cell) therapy represents a paradigm shift in treating refractory hematological malignancies. Despite its transformative potential, clinical application is frequently complicated by severe, potentially life-threatening toxicities, with cytokine release syndrome (CRS) being the most prominent. This comprehensive review synthesizes current therapeutic strategies for CRS, integrating recent advancements in multidisciplinary care models, refined risk stratification, and evolving prophylactic protocols. Furthermore, this paper contextualizes CRS management within the broader landscape of CAR T-cell-related adverse event (AE) mitigation, highlighting established best practices and exploring future directions aimed at enhancing the safety profile and optimizing the therapeutic index of CAR T-cell therapies.
Cutaneous immune-related adverse events caused by immune checkpoint inhibitors are among the earliest and most common adverse reactions during tumor immunotherapy, resulting in substantial physical and psychological distress for patients. In severe cases, delayed or non-standard treatment may lead to life-threatening complications. The clinical manifestations of cutaneous immune-related adverse events are diverse and complex; considerable uncertainty exists regarding their diagnosis and management, including whether to discontinue tumor immunotherapy. This consensus provides a systematic analysis, comprehensive evaluation, and recommendations on the classification, clinical presentation, and treatment of cutaneous immune-related adverse events, as well as guidance concerning whether tumor immunotherapy should be discontinued. Emphasis is placed on the fact that immune-related adverse events often affect multiple organs and systems. Therefore, clinical assessments should extend beyond cutaneous involvement to include potential complications affecting the heart, lungs, endocrine system, and digestive system.
The ABC transporter gene family, pivotal in multidrug resistance and tumor progression, exhibits extensive alternative splicing (AS) events with potential clinical implications in pan-cancer prognosis and therapy. This study investigates the causal relationship between ABC transporter AS events and cancer risk, integrating multi-omics analysis with Mendelian randomization (MR) and Bayesian Weighted MR (BWMR) to explore their role in tumor immunology and prognosis.
Transcriptomic data from TCGA and GWAS were analyzed to identify AS events in 114 ABC transporter genes across 33 cancers. A multifactorial Cox prognostic model was constructed, validated via LASSO regression, and evaluated for immune infiltration using ssGSEA and TIMER. SF-AS regulatory networks were mapped via Cytoscape, and causal inferences were tested using MR and BWMR.
Eleven AS genes (e.g., PSMA4, PSMD7) were linked to pan-cancer prognosis, with high-risk patients showing elevated immune infiltration (CD8 + T cells, B cells) and checkpoint gene expression (CD274, CTLA4). The SF-AS network revealed 50 splicing factors regulating 17 AS events. MR confirmed UBA52 (protective) and ABCB4 (risk) as causally associated with pan-cancer, corroborated by BWMR. The nomogram model predicted survival with moderate accuracy (AUC: 0.695–0.756).
This study establishes a causal link between ABC transporter AS events and pan-cancer risk, highlights their interplay with immune checkpoints, and proposes novel biomarkers for prognosis and immunotherapy. MR/BWMR validation underscores the potential of AS signals in guiding targeted therapies.
Chimeric antigen receptor-T (CAR-T) cell therapy has revolutionized cancer immunotherapy, enlightening new hope for patients with hematological malignancies and emerging potential in solid tumors and other refractory diseases. This review delves into the fundamentals, challenges, technological innovations, clinical breakthroughs, and future prospects of CAR-T cell therapy. It explores the mechanisms of action, evolution, key challenges such as toxicity and solid tumor resistance, recent technological advancements in CAR engineering, clinical breakthroughs in solid tumors and other refractory diseases, and future directions including next-generation constructs, gene editing, manufacturing scalability, and expansion beyond cancers. By synthesizing the latest research, this review aims to provide a comprehensive understanding of CAR-T cell therapy and its potential to transform cancer treatment and other therapeutic areas.
To present the clinical course and outcome of a patient with advanced hepatocellular carcinoma (HCC) who received HBsAg-targeted T cell receptor-engineered T cells (TCR-T).
A 61-year-old man with advanced HCC developed cytokine release syndrome (CRS) after HBsAg-targeted TCR-T infusion, which met grade 3 criteria within 24 h and then rapidly improved to grade 2, alleviated after two weeks. Although hematologic toxicities were prominent, recovery was achieved and there were no severe consequences. At 6 weeks post-infusion, the patient's cervical lymph nodes and pulmonary metastases showed slight reduction, suggesting a possible transient therapeutic effect. However, by day 87 post-infusion, all lesions had progressed again. Meanwhile, the bone metastases demonstrated continuous progression.
HBsAg-targeted TCR-T cell therapy may represent a potential therapeutic strategy for advanced HCC, demonstrating a manageable safety profile when carefully monitored for ≥ Grade 3 cytokine release syndrome and hematological toxicities.
Melanoma is a highly aggressive malignancy originating from melanocytes. Patients with advanced melanoma have a poor prognosis, with a high risk of distant metastasis and resistance to targeted therapy or immunotherapy. In recent years, adoptive cell therapy (ACT), an emerging personalized immunotherapy, has made significant progress in the treatment and investigation of melanoma. This review provides a comprehensive overview of ACT in melanoma, emphasizing its current application, therapeutic benefits, prevailing challenges, and future prospects, with particular focus on four major strategies: tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T cells (CAR-T), T cell receptor-engineered T cells (TCR-T), and other immune cell-based therapies. With continuous evolution of bioengineering and precision medicine, ACT holds increasing potential for treating melanoma and other solid tumors, offering new avenues for clinical translation.
Pyroptosis, an important form of cell death, remains to be explored for its significance in renal cell carcinoma.
We conducted a Summary-data-based Mendelian Randomization (SMR) analysis to investigate the association between pyrogenic gene-related SNPs and renal cell carcinoma outcomes, identified core genes with significant associations, and then performed transcriptomic profiling analysis of renal clear cell carcinoma using TCGA data to assess diagnostic and prognostic potential. Subsequently, we explored the functional mediation of core genes through enrichment analysis and GSEA, and analyzed immune function using Cibersort and ssGSEA. We then presented the expression patterns of core genes using single-cell data, and finally analyzed the differences in chemotherapy sensitivity between high- and low-expression groups of core genes using oncoPredict, and validated the potential for targeting core genes with molecular drugs.
Through SMR and MR, we identified CASP9 as a key factor in pyroptosis-related processes in renal cell carcinoma, acting as a protective factor for renal cell carcinoma outcomes and demonstrating excellent diagnostic potential. Survival analysis revealed that high CASP9 expression in early-stage renal cell carcinoma was associated with better prognosis, whereas the opposite was true in advanced-stage renal cell carcinoma. Functional enrichment analysis indicated that CASP9 may mediate multiple pathways, including epithelial-mesenchymal transition. Immune infiltration analysis highlighted a strong correlation between CASP9 expression and natural killer cell abundance. Finally, we analyzed differences in chemotherapy sensitivity between high- and low-CASP9 expression groups and identified potential drugs for molecular docking validation.
CASP9 can serve as a potential target for renal clear cell carcinoma, with potential for guiding diagnosis, prognosis, and chemotherapy selection.