This study aimed to investigate whether patients with stage IB NSCLC could benefit from adjuvant chemotherapy.
In the years 2010 to 2015, 1,829 NSCLC patients with stage IB disease were chosen from the SEER database. To equalize the baseline characteristics between the surgery plus adjuvant chemotherapy group (intervention) and the surgery alone group (control), propensity score matching (PSM) was used. The log-rank test plotted Kaplan–Meier survival curves to compare the overall survival (OS) and disease-specific survival (DSS). Cox proportional hazard regression was used to perform univariate and multivariate analysis on overall survival.
One hundred ninety-seven patients in each group with a mean follow-up period of 65.4 months were enrolled after PSM. A significant benefit in overall survival ([intervention vs. control] HR = 0.72; 95% CI: 0.54 to 0.94; P = 0.026) was detected in the intervention group before PSM. And there were significantly improved OS (HR = 0.63; 95% CI: 0.42 to 0.92; P = 0.036) and DSS (HR = 0.73; 95% CI: 0.52 to 0.95; P = 0.044) for the patients with visceral pleural invasion (VPI) in the intervention group compared with the control group. After PSM, the patients with VPI in the intervention group had better overall survival (HR = 0.69; 95% CI: 0.40 to 0.98; P = 0.048) than those in the control group. The Cox proportional hazard regression analysis showed that VPI (HR = 1.29; 95% CI: 1.11 to 1.54; P < 0.001) was also an independent prognostic factor.
Stage IB NSCLC with VPI could benefit from adjuvant chemotherapy after R0 resection.
Nine decades ago in 1933, Evarts A. Graham performed the first successful pneumonectomy in a patient with primary pulmonary squamous cell carcinoma. The patient survived for another 30 years, which drew the curtain on the surgical treatment of lung cancer. Surgical resection continues to be the cornerstone of multidisciplinary treatment for patients with early-stage non-small cell lung cancer and a proportion of those with locally advanced disease. Moreover, recent years have seen developments in automatic control, biomechanics, robotics, image transmission, artificial intelligence, three-dimensional reconstruction and printing, biological pharmacy, and molecular biology. Therefore, there is now an increasing focus on how to integrate these technologies into lung cancer surgery to improve quality of life, resect the tumor accurately, expand the population that is suitable for surgical management, predict disease recurrence with better accuracy, and ultimately achieve long-term survival. This article systematically reviews the innovative achievements that may be detrimental to current clinical practice and in future clinical trials, and simultaneously provides a brief overview of the polyvagal perspective in this field.
Lung cancer, of which non-small-cell lung cancer (NSCLC) is the most common type, is the leading cause of cancer-related deaths. Anatomic pulmonary resection followed by adjuvant chemotherapy is considered the standard-of-care for patients with resectable NSCLC; however, postoperative relapses and metastases remain common. Immunotherapy, mainly with immune checkpoint inhibitors, has revolutionized the treatment of patients with metastatic NSCLC. In addition, it provides a new strategy for the perioperative treatment of resectable NSCLC. Initial encouraging results have been reported from clinical studies exploring different immunotherapeutic strategies for resectable NSCLC. This review summarizes the results of the latest clinical trials evaluating various perioperative immunotherapeutic approaches aimed at improving the outcomes of patients with resectable NSCLC.
To explore surgical treatment strategies for thymic tumors invading the superior vena cava (SVC).
Fifty-seven patients were identified to have undergone surgery at our institution for thymic tumors invading the SVC from January 2016 to June 2021. The tumors were classified based on the involvement of the SVC as follows: type I, only the left or right innominate vein involved, so the patient underwent resection only without revascularization (n = 25); type II, less than 30% of the SVC circumference involved, so the patient underwent direct resection followed by repair of the SVC defect (n = 2); and type III, more than 30% of the SVC circumference involved, so the patient underwent single conduit reconstruction between the innominate vein and right atrial appendage first followed by extended resection of the tumor and the invaded portion of the SVC (n = 30).
Complete resection was achieved in all patients. Most patients (54/57) had high-risk thymoma or thymic carcinoma. No serious complications occurred in patients with type I or type II tumors. Three of the 30 patients with type III tumors died, two required repeat surgery, one experienced a myasthenia gravis crisis, and one developed a surgical site infection. The median follow-up duration was 22 months. The 5-year progression-free survival and overall survival rates were 59.6% and 81.2%, respectively.
This typing method can be used to guide selection of the surgical strategy for a thymic tumor involving the SVC. A strategy of single-vessel reconstruction before extensive resection is appropriate for patients with a type III tumor.
Lung adenocarcinoma (LUAD) is a common cancer with a poor prognosis. Platelet-activating factor acetylhydrolase, isoform Ib, gamma subunit 29 kDa (PAFAH1B3) plays an important role in the development of many types of human malignancies. However, the precise role and mechanisms of PAFAH1B3 in LUAD are still unknown.Therefore, we will initially explore the effect of PAFAH1B3 on LUAD in this study.
In this study, we first performed a pan-cancer analysis of PAFAH1B3 expression and prognosis using The Cancer Genome Atlas (TCGA), genotype-tissue expression (GTEx) data, and GEPIA database. Next, the relationship between PAFAH1B3 expression and LUAD immune infiltration and pyroptosis-related genes was explored by GEPIA database and TIMER database. The effect of PAFAH1B3 on LUAD was further explored by CCK-8, wound healing, and Transwell assays. Finally, non-coding RNA (ncRNA) that may be involved in the regulation of PAFAH1B3 was explored using Starbase database analysis.
The results found that PAFAH1B3 may be an oncogene in LUAD and has a significant adverse relationship with tumor immune cell infiltration, immune cell biomarkers and pyroptosis-related gene expression. Meanwhile, cell experiments also found that PAFAH1B3 knockout significantly reduced the proliferation, migration and invasion of A549 cells.
PAFAH1B3 high expression in LUAD patients is associated with poor prognosis, tumor immune infiltration, and cell pyroptosis gene expression.
The liver, the largest solid organ in the body, is susceptible to metabolic diseases and malignant tumors. Studying its physiological and pathological processes helps to optimize the clinical treatment. Organoids are a novel tool for studying physical development, disease mechanisms, and high-throughput drug screening due to their similarity in composition, structure, and function to internal organs. Recent studies have shown that stem cells, hepatocytes, or cholangiocytes can form “liver organoids” under the synergistic action of specific extracellular matrix and various signaling molecules. This review outlines techniques for generating liver organoids that maximally recapitulate the liver structure and functions in vitro and thoroughly discusses the customary applications of organoids derived from liver tissue, induced pluripotent stem cells (iPSCs) and liver tumors. In this review, a meticulous analysis is provided of the comparatively advanced culture systems used in the construction of liver cancer-derived organoids. Additionally, we reviewed the progress of liver organoids in disease modeling, drug efficacy, and toxicity evaluation, in hopes of generating innovative ideas for the research and applications of liver organoids.
Combining surgery and perioperative adjuvant therapy, including tyrosine kinase inhibitors (TKI), anti-PD-1 antibody, and interventional therapy, can prolong the survival of patients with advanced hepatocellular carcinoma (HCC). Adverse reactions to adjuvant therapy, surgical trauma, and surgical complications are challenging for this combined treatment mode. This study aims to explore whether minimally invasive hepatectomy is safe or appropriate in patients with advanced HCC.
This retrospective study involved patients with advanced HCC who underwent minimally invasive surgery (MIS group, n = 31) or open surgery (OS group, n = 35) from August 2020 to April 2023 from four medical groups at two medical centers. Operation-related indicators, early postoperative complications, and postoperative drug tolerance were compared between the two groups.
Sixty-six patients were enrolled. Between the MIS group and the OS group, there were no significant differences in Barcelona Clinic Liver Cancer (BCLC) tumor staging (P = 0.44), surgical difficulty (P = 0.29), and R0 resection rate (P = 0.34). Compared with the OS group, the MIS group had less blood loss (101.9 mL vs. 209.0 mL, P = 0.003), shorter average operation time (165.7 min vs. 224.5 min, P = 0.000 4), shorter postoperative fasting time (1.5 d vs. 2.4 d, P = 0.002), shorter postoperative bed time (1.7 d vs. 3.0 d, P < 0.0001) and length of hospital stay (7.1 d vs. 9.4 d, P = 0.001), lower incidence of complication (Clavien-Dindo grade II–III, P = 0.03), better nutritional status, and earlier postoperative adjuvant treatment.
Minimally invasive hepatectomy is safe for patients with advanced HCC after conversion therapy and may improve tolerance to combination treatment relative to open surgery.
Identification of prognostic biomarkers for outcomes in gastrointestinal (GI) cancer with immunotherapy is important. This study investigated the relationship between the prognostic biomarker, pretreatment neutrophil-to-lymphocyte ratio (preNLR), and immunotherapeutic outcomes in patients with advanced GI cancer.
We searched the PubMed, Embase, and Cochrane Library databases for studies reporting predictive values for preNLR in patients with advanced GI cancer treated with immune checkpoint inhibitor (ICI). The primary outcomes considered were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were pooled using a random effects model. We then validated the results observed in an in-house cohort of patients treated with ICIs for advanced GI cancers. Other prognostic factors for PFS and OS were explored using Cox proportional hazard analyses.
Overall, 27 observational studies involving 3,610 patients with advanced GI cancer were included. Patients with higher preNLR were associated with poorer PFS (HR 1.70, 95% CI 1.50–1.92) and OS (HR 2.35, 95% CI 1.82–3.03) with ICI treatment. Subgroup analyses based on NLR cut-off value, research center, sample size, and ICI drugs used were consistent with the primary results. A retrospective analysis of the in-house patient cohort validated these results (PFS: HR 3.173, 95% CI 2.314–4.351; OS: HR 3.004, 95% CI 1.837–4.912). Multivariable Cox regression analysis of 174 patients showed that higher preNLR and negative programmed death ligand-1 (PD-L1) expression were independently, significantly, and unfavorably associated with PFS and OS.
PreNLR might be an effective prognostic biomarker for patients with advanced GI cancer treated with ICIs.
Gastric cancer (GC), a molecularly and phenotypically highly heterogeneous malignancy, is a leading cause of cancer-related deaths. The Cancer Genome Atlas (TCGA) project identifies the microsatellite instability (MSI) subtype of GC, which has garnered increasing attention due to its relatively favorable survival outcome and better response to immune checkpoint inhibitors (ICIs). The occurrence of MSI is closely associated with the defects in mismatch repair system, subsequently leading to the accumulation of mutations in cell genome, particularly in microsatellites. Based on the exclusive features of MSI GC, several detection methods like immunohistology have been developed to determine MSI status clinically, with novel detection methods developing. It is clinically observed that MSI GC tends to have a better response to ICIs treatment while its response to chemotherapy is controversial, necessitating further investigation into the underlying mechanisms. In this review, we systemically summarized the molecular features, detection method, clinico-pathological characteristics and prognosis of MSI GC, offering a comprehensive overview of this unique GC subtype.
Tumor research is a fundamental focus of medical science, yet the intrinsic heterogeneity and complexity of tumors present challenges in understanding their biological mechanisms of initiation, progression, and metastasis. Recent advancements in single-cell transcriptomic sequencing have revolutionized the way researchers explore tumor biology by providing unprecedented resolution. However, a key limitation of single-cell sequencing is the loss of spatial information during single-cell preparation. Spatial transcriptomics (ST) emerges as a cutting-edge technology in tumor research that preserves the spatial information of RNA transcripts, thereby facilitating a deeper understanding of the tumor heterogeneity, the intricate interplay between tumor cells and the tumor microenvironment. This review systematically introduces ST technologies and summarizes their latest applications in tumor research. Furthermore, we provide a thorough overview of the bioinformatics analysis workflow for ST data and offer an online tutorial (https://github.com/SiyuanHuang1/ST_Analysis_Handbook). Lastly, we discuss the potential future directions of ST. We believe that ST will become a powerful tool in unraveling tumor biology and offer new insights for effective treatment and precision medicine in oncology.
Primary liver cancer, predominantly hepatocellular carcinoma (HCC), remains to be a significant public health challenge in China. Drug therapy continues to be a cornerstone in the treatment of HCC. Notably, recent breakthroughs in immunotherapy, exemplified by immune checkpoint inhibitors, have introduced innovative avenues for pharmacological intervention. Chinese researchers have undertaken extensive investigations into this therapeutic pathway, focusing particularly on its applications in neoadjuvant and transitional therapies, as well as postoperative adjuvant treatments. These endeavors have yielded promising therapeutic outcomes, showcasing the potential of immunotherapy across various aspects of HCC management. In addition to therapeutic advancements, researchers have made notable progress in understanding the complexities of HCC, particularly in deciphering tumor heterogeneity and the mechanisms underlying tumor recurrence and metastasis. Leveraging cutting-edge methodologies such as spatiotemporal omics and clinical cross-omics, these researchers have gained deeper insights into the disease's biology. These fundamental discoveries have solidified the theoretical basis for future precision medicine approaches in HCC treatment. This article aims to comprehensively summarize these pivotal research advancements across both basic and clinical research fields.
To establish a prognostic model to predict the survival of patients with esophageal cancer (EC).
We extracted the expression profiles of prognostic-related genes and clinicopathological data from TCGA and GEO databases. Subsequently, a comprehensive bioinformatics analysis was conducted to construct a prognostic model utilizing LASSO and multivariate Cox regression. The stability of the risk signature was validated through Kaplan-Meier and ROC curve analyses on the training, internal testing, and external testing sets. Furthermore, we developed a nomogram that incorporates the risk score and clinical features to predict the suvival. Additionally, a nomogram incorporating the risk score and relevant clinical parameters was developed to enhance survivorship prediction. Furthermore, we delved into exploring the correlation between the risk score and immune cell abundance, expression of cancer checkpoints, as well as responses to immunotherapy and chemotherapeutic agents.
In this study, we successfully identified 19 prognosis-related genes out of a pool of 65 PANoptosis-related genes (PRGs) sourced from existing literature. Through consensus clustering analysis, we classified patients into two distinct groups as PANcluster A and B. Furthermore, the risk score derived from the five PANoptosis-related signatures emerged as an independent prognostic factor among patients with EC. To enhance the prognostic accuracy, we devised a nomogram integrating the risk score with clinical risk characteristics, enabling the prediction of 1-year, 2-year, and 3-year overall survival (OS) rates. Notably, individuals classified in the high-risk group demonstrated poorer prognoses compared to their low-risk counterparts. Furthermore, the risk score displayed substantial correlations with immune cell abundance, expression levels of cancer checkpoints, and responses to immunotherapy and chemotherapeutic agents. These pivotal findings underscore the significance of considering PANoptosis-related patterns in improving prognostic assessment and predicting treatment responses in patients diagnosed with esophageal cancer.
We constructed a reliable prognostic risk model for EC utilizing five PRGs. The developed nomogram serves as a valuable tool in predicting patient outcomes, offering crucial insights that can inform and guide treatment decisions for individuals diagnosed with EC.
MIR99AHG, a recently discovered long non-coding RNA (lncRNA), serves as the host gene for the miR-99a/let-7c/miR-125b-2 miRNA cluster. The intricate processing of its three introns yields three distinct micro RNAs (miRNAs). Experimental evidence highlights significant variations in MIR99AHG expression across various cancer types, indicating its potential as a diagnostic marker for cancer. Moreover, FOXA1 acts as an upstream regulator, actively promoting MIR99AHG expression. MIR99AHG, in turn, regulates five downstream proteins (ANXA2, PTBP1, MMP9, PBX3, and PHB2), as well as three competing endogenous RNA (ceRNA) axes and three signaling pathways. This broad spectrum of regulatory effects underscores the pivotal role of MIR99AHG in shaping the behavior of cancer cells. In cancer treatment, MIR99AHG's functions are equally noteworthy. Experimental findings suggest its impact on immune cell activity within the tumor micro-environment and its role in modulating cancer cell resistance to chemotherapeutic drugs. Follow-up studies on patients further confirm the close association between high MIR99AHG expression and poor prognosis across various cancers, exhibiting significant statistical correlations with various pathological behaviors. In summary, MIR99AHG, acting as a multifaceted lncRNA, not only introduces a potential novel marker for cancer diagnosis but also demonstrates significant application value in cancer treatment and prognosis evaluation.
Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer with a high mortality rate. Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets. This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization (MR) and colocalization analyses.
Proteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics. Summary-level data for LUSC were obtained from the ILCCO Consortium, the FinnGen study, and a separate GWAS study. A total of 1,046 shared protein quantitative trait loci (pQTLs) were analyzed. Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations.
MR analysis identified six plasma proteins associated with LUSC risk: HSPA1L, PCSK7, POLI, SPINK2, TCL1A, and VARS. HSPA1L (OR = 0.47; 95% CI: 0.34–0.65; P = 4.89 × 10–6), SPINK2 (OR = 0.68; 95% CI: 0.58–0.80; P = 3.17 × 10–6), and VARS (OR = 0.44; 95% CI: 0.31–0.63; P = 5.94 × 10–6) were associated with a decreased risk of LUSC. Conversely, PCSK7 (OR = 1.37; 95% CI: 1.21–1.56; P = 1.40 × 10–6), POLI (OR = 4.50; 95% CI: 2.25–9.00; P = 2.13 × 10–5), and TCL1A (OR = 1.72; 95% CI: 1.34–2.21; P = 1.89 × 10–5) were associated with an increased risk. The SMR analysis and HEIDI test confirmed the robustness of these associations. HSPA1L, SPINK2, and VARS showed significant inverse associations, with strong colocalization evidence for TCL1A (PPH4 = 0.817).
This study identified six plasma proteins potentially causal for LUSC risk. HSPA1L, SPINK2, and VARS are associated with decreased risk, while PCSK7, POLI, and TCL1A are linked to increased risk. These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention.
MyD88 was initially discovered to be upregulated during interleukin (IL)-6-induced myeloid differentiation in the 1990s. Subsequent studies have identified it as a typical adapter for inflammatory signaling pathways downstream of members of the Toll-like receptor (TLR) and IL-1 receptor families. MyD88 is profoundly involved in the NF-κB and its associated signaling pathways, which contribute to the proliferation and survival of B cells. The downstream products of MyD88's involvement in the pathway also define it as a key link of the inflammatory pathway. This suggests that MyD88 plays a vital role in the emergence and growth of both hematologic and solid tumors. In this review, we focus on the role of MyD88 in signaling pathways and explore its impact on tumors.
Cutaneous angiosarcoma is a malignant, aggressive, vascular tumor that usually arises in association with prior radiation and chronic lymphedema. A primary cutaneous angiosarcoma originating in the scrotum is extremely rare, with few previous cases reported in the literature.
We report a 43-year-old man who presented with a unilateral scrotal lesion. The diagnosis of cutaneous angiosarcoma was confirmed by microscopic examination which revealed multiple vascular spaces lined by atypical cells, wide areas of necrosis were also seen. Immunohistochemistry showed strong positivity for ERG, focal positivity for CD31, and negative staining for CK, CD34, desmin, S100, SMA, and HHV8. Excision of the right hemiscrotum was performed with no evidence of local recurrence or metastasis in the following eleven months.
This is the first reported case of primary scrotal cutaneous angiosarcoma without identifiable risk factors. Despite its rarity, cutaneous symptoms on the scrotum should be investigated for the potential of a scrotal angiosarcoma.
Hepatocellular carcinoma (HCC) is a malignant tumor associated with high global incidence and mortality rates. Proteomics, as a platform technology of cellular protein expression, modification, and interaction, has provided innovative perspectives on early diagnosis, treatment, and targeted drug development for HCC. This review summarizes recent progress in proteomics for advancing HCC biomarker discovery, drug target identification, and understanding drug action mechanisms. Proteomic technologies, including mass spectrometry for specific protein signatures identification, protein microarrays for high-throughput analysis, and bioinformatics for data interpretation, have profoundly promoted the identification of liver cancer-specific biomarkers. These advancements not only facilitate early diagnosis but also improve prognostic assessment. Proteomics is pivotal in expediting the discovery and development of new drugs, providing more effective and personalized treatment options for HCC patients. This review offers a comprehensive overview of the applications of proteomics in anti-HCC drug research, serving as a reference to further advance the development of HCC research and treatment domains.