J Cancer [JOURNAL]
Sun
200 papers
A CRM-Integrated ypT Staging System Improves Prognostic Stratification Following Neoadjuvant Therapy in Rectal Cancer.
Chow WH, Ho CH, Chen YC … +2 more , Huang HY, Yang CC
J Cancer · 2026 · PMID 41869440 · Full text
INTRODUCTION: The ypT staging system has limited prognostic value after neoadjuvant therapy, as it primarily reflects only tumor characteristics alone. This study proposes a novel staging system that integrates circumfer...
INTRODUCTION: The ypT staging system has limited prognostic value after neoadjuvant therapy, as it primarily reflects only tumor characteristics alone. This study proposes a novel staging system that integrates circumferential resection margin (CRM) status with the ypT category to enhance prognostic accuracy following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. METHODS: We analyzed data from 4,308 rectal adenocarcinoma patients treated with nCRT followed by surgery, using the Taiwan Cancer Registry and National Health Insurance Research Database (2011-2021). CRM involvement was defined as a margin ≤1 mm. Overall survival was assessed using multivariable Cox regression, and prognostic performance of the proposed CRM-integrated ypT staging system was compared with the American Joint Committee on Cancer (AJCC) TNM system using Harrell's c-statistic. RESULTS: CRM involvement (≤1 mm) was significantly associated with worse 5-year survival (adjusted odds ratio, 0.44; 95% CI, 0.31-0.61). Due to the low rate of CRM positivity in ypT0-2 patients, a modified ypT classification was established: new ypT3 (ypT3 and CRM-), new ypT4A (ypT4A and CRM-), new ypT4B (ypT3 and CRM+ or ypT4B and CRM-), and new ypT4C (ypT4A and CRM+ or ypT4B and CRM+). This system demonstrated better prognostic discrimination than the current AJCC classification (Harrell's c-statistic: 0.756 vs. 0.752, P = 0.034). CONCLUSIONS: Incorporating CRM into the ypT stage offers survival stratification and may guide more individualized postoperative treatment strategies for rectal cancer patients after nCRT.
Proteasome Assembly Chaperone 3 Defines Metabolic-Immune Programs and Poor Prognosis in Breast Cancer via Multi-Omics Approaches.
Kumar S, Ta HDK, Yang HC … +12 more , Shih CL, Solomon DD, Ko CC, Xuan DTM, Lee YK, Chang KF, Lin HR, Kao SH, Chuang JY, Chen JB, Wang CY, Nguyen NUN
J Cancer · 2026 · PMID 41869439 · Full text
The proteasome assembly chaperone () gene family (comprised of , , , and ) plays a critical role in proteasome biogenesis; however, its involvement in breast cancer remains poorly understood. Among these chaperones, is...
The proteasome assembly chaperone () gene family (comprised of , , , and ) plays a critical role in proteasome biogenesis; however, its involvement in breast cancer remains poorly understood. Among these chaperones, is uniquely and markedly elevated in breast cancer and is associated with poor clinical outcomes. We systematically investigated the roles of family genes in breast cancer by integrating multi-cohort genomic and transcriptomic datasets, including TCGA-BRCA, METABRIC, and multiple NCBI GEO cohorts. Comprehensive bioinformatics analyses were performed using bulk RNA sequencing and single-cell RNA sequencing data. A gene set enrichment analysis (GSEA) and immune infiltration analyses (CIBERSORT and TIMER) were applied to characterize dysregulated biological pathways, tumor microenvironmental features, and clinical relevance. In addition, molecular docking analyses were conducted to assess the druggability and binding potential of PSMG family proteins with selected small-molecule inhibitors. Elevated PSMG3 expression was consistently associated with poor survival outcomes across multiple breast cancer cohorts. Functional enrichment analyses revealed that PSMG3-high tumors were characterized by activation of hypoxia-related signaling pathways and dysregulated fatty acid metabolism, suggesting a role for PSMG3 in metabolic reprogramming. Immune deconvolution analyses further demonstrated significant correlations between PSMG3 expression and distinct immune cell populations within the tumor microenvironment. These findings were supported by single-cell transcriptomic profiling, which revealed subtype-specific expression patterns of PSMG3 in malignant epithelial cell populations. This integrative multi-omics analysis identified PSMG3 as a clinically relevant proteasome assembly chaperone associated with aggressive breast cancer phenotypes, metabolic dysregulation, and tumor immune contexture. Collectively, these results highlight PSMG3 as a promising prognostic biomarker and potential therapeutic target in breast cancer.
Fluid-Derived Organoids from Pleural Effusion and Ascites: Emerging Models for Drug Resistance and Personalized Oncology.
Chen Y, Xu X, Chen J … +5 more , Yin M, Chen J, Qi Z, Shi M, Su W
J Cancer · 2026 · PMID 41869438 · Full text
Malignant pleural effusion (MPE) and malignant ascites (MA) are common complications in advanced-stage cancers, often signifying disease progression and resistance to treatment. Compared to tissue biopsies or surgical sp...
Malignant pleural effusion (MPE) and malignant ascites (MA) are common complications in advanced-stage cancers, often signifying disease progression and resistance to treatment. Compared to tissue biopsies or surgical specimens, materials derived from effusions offer advantages such as minimal invasiveness, ease of accessibility, and the feasibility of repeated collection during therapeutic interventions. Organoids generated from tumor cells in effusions, termed fluid-derived organoids (FDOs), have demonstrated the ability to maintain genetic heterogeneity and accurately replicate patient-specific tumor phenotypes. These characteristics position FDOs as promising models for investigating drug resistance mechanisms and informing personalized oncology strategies. In the context of lung cancer, organoids derived from pleural effusions have been employed to study acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and immunotherapy. Similarly, in ovarian and gastrointestinal cancers, organoids derived from ascites have proven to be valuable platforms for examining chemotherapy resistance and conducting drug sensitivity testing. FDOs have shown significant potential for translational applications by effectively correlating drug responses with clinical outcomes, thus facilitating real-time monitoring of resistance evolution. However, several challenges remain, such as achieving culture standardization, maintaining the integrity of tumor microenvironment components, and integrating with multi-omics approaches. This review provides a comprehensive overview of recent advancements in the use of pleural effusion- and ascites-derived organoids for drug resistance research, underscores their applications in personalized oncology, and explores future research directions.
Association Between Long-term Use of H Receptor Antagonists and Prostate Cancer Risk: A Case-Control Study in Taiwan.
Wang SF, Liu YC, Nguyen PA … +4 more , Lin GL, Huang CW, Rahmanti AR, Yang HC
J Cancer · 2026 · PMID 41584050 · Full text
The association between long-term use of histamine-2 receptor antagonists and prostate cancer remains unclear. This study aimed to examine the age-specific risk of prostate cancer associated with long-term use of these m...
The association between long-term use of histamine-2 receptor antagonists and prostate cancer remains unclear. This study aimed to examine the age-specific risk of prostate cancer associated with long-term use of these medications. We conducted a nationwide case-control study using Taiwan's Health and Welfare Data Science Center database from 2003 to 2016. Men with newly diagnosed prostate cancer were matched to controls, and long-term use was defined as cumulative exposure of sixty days or more. Adjusted odds ratios were estimated using conditional logistic regression, controlling for comorbidities and medications. Among 43,578 prostate cancer cases and 174,312 controls, long-term use of histamine-2 receptor antagonists was associated with a modest increase in prostate cancer risk, significant in men aged sixty-five and older (adjusted odds ratio = 1.087, 95% CI: 1.044-1.131) but not in younger groups. Cimetidine and ranitidine were each associated with increased risk in older men, while famotidine showed no significant association across age groups. Notably, cimetidine uses in men aged forty to sixty-four was associated with reduced prostate cancer risk (adjusted odds ratio = 0.865, 95% CI: 0.755-0.990), suggesting possible age-dependent effects. These findings suggest that long-term use of cimetidine and ranitidine may increase prostate cancer risk in older men, while famotidine was not associated with prostate cancer risk. Risk varies by age and drug type, highlighting the need for drug-specific evaluation in cancer pharmacoepidemiology.
Comparative Blood-Based Transcriptomic Profiles of Prostate Cancer Patients from South Africa and the USA: A Cross-Sectional Pilot Study.
Koduru SV, Kidd M, Pieters A … +3 more , Nagel SE, Millar RP, Halim AB
J Cancer · 2026 · PMID 41584049 · Full text
Prostate cancer (PCa) is a major health problem worldwide with variable incidence, progression and outcomes depending on genetic, environmental and socio-economic factors. This study compares gene expression profiles in...
Prostate cancer (PCa) is a major health problem worldwide with variable incidence, progression and outcomes depending on genetic, environmental and socio-economic factors. This study compares gene expression profiles in PCa patients from South Africa (RSA) and the United States (USA) using RNA sequencing in whole blood and pathway analyses. Whole blood samples were collected in Wren RNA stabilization tubes from RSA-PCa ( = 6), RSA-controls ( = 6), USA-PCa ( = 7) and USA-Controls ( = 11). RNA sequencing revealed 1,627 differentially expressed genes (DEGs) in RSA-PCa vs. RSA-controls, and 2,193 DEGs in USA-PCa vs. USA-Controls. Pathway analyses identified geographical region-specific variations; RSA-PCa had upregulated myeloid suppressor cell pathways and immunosuppressive markers while USA-PCa samples exhibited upregulated cytokine signaling and inflammatory pathways. Comparative analysis of healthy controls revealed 2,280 DEGs, which indicated significant differences in molecular profile of the geographic locations. qRT-PCR undertaken on 27 biomarkers related to PCa in whole blood (PROSTest) identified that 26 (96%) of the marker genes were commonly expressed. RNAseq and normalized PCR gene expression of these markers were well-correlated (r = 0.44, = 0.0012, = 30 pairs). The results of this study indicate that there are geographic differences in blood-based gene expression in both controls and individuals with PCa. Genes associated with a clinically validated molecular assay (PROSTest) were identified in both populations, but significant differences in gene expression relevant to tumor pathobiology were identified. These immune-associated signaling pathways suggest differences between these two cohorts in blood-based molecular architecture related to PCa. They also suggest the need to consider population-specific biomarkers to better understand this disease. Ultimately, optimizing blood-based molecular diagnostic and therapeutic approaches will require population-level studies.
Single-cell and transcriptomic profiling reveal stemness-driven immune evasion in obstructive sleep apnea (OSA) associated lung cancer.
Liu YW, Wu CJ, Chang KF … +16 more , Lee YK, Lin HR, Ko CC, Hsieh CB, Chang CH, Lin CH, Chen BS, Solomon DD, Kumar S, Palekkode N, Fathima A, Xuan DTM, Nguyen NUN, Waikhom J, Yuan CH, Wu YJ
J Cancer · 2026 · PMID 41584048 · Full text
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to i...
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer.
Complement and Coagulation Cascades Pathway was Inactivated in HIV-Associated Colorectal Cancer: Results from a Proteomics Study.
Lian S, Li L, Yang Y … +3 more , Liu S, Song S, Zhang L
J Cancer · 2026 · PMID 41584047 · Full text
: Colorectal cancer (CRC) remains a leading cause of global cancer-related morbidity and mortality. Human Immunodeficiency Virus (HIV)-1 infection worsens colorectal cancer (CRC) outcomes. : To investigate mechanisms, we...
: Colorectal cancer (CRC) remains a leading cause of global cancer-related morbidity and mortality. Human Immunodeficiency Virus (HIV)-1 infection worsens colorectal cancer (CRC) outcomes. : To investigate mechanisms, we conducted Tandem Mass Tag proteomics on tumor (C) and adjacent normal tissues (A) from five HIV-positive (HIV+) and four HIV-negative (HIV-) CRC patients. Four comparisons were analyzed: HIV+C vs HIV+A (differentially expressed proteins, (DEPs)-1), HIV-C vs HIV-A (DEPs-2), HIV+A vs HIV-A (DEPs-3), HIV+C vs HIV-C (DEPs-4) (|fold change| ≥ 2, p < 0.05). The DEPs specifically affected by HIV (DEPs-5) underwent KEGG pathway enrichment analysis. The relative abundance of pathway-associated DEPs was compared with the data from CPTAC database. Key DEPs were validated by western blot/immunohistochemistry. : We identified 749 (DEPs-1), 431 (DEPs-2), 4 (DEPs-3), and 21 (DEPs-4) DEPs. After excluding DEPs common to other comparisons, 592 HIV-specific DEPs (410 up-, 182 downregulated) were identified. KEGG enrichment revealed top altered pathways: upregulated ribosome (40 proteins) and downregulated complement and coagulation cascades (CCC pathway; 24 proteins). Comparison with the CPTAC database showed that HIV infection significantly increased the expression of upregulated DEPs but only slightly decreased the expression of downregulated ones. Downregulation of key CCC pathway proteins (C8B and SERPINA1) was confirmed by western blot and immunohistochemistry, respectively. : HIV-associated CRC exhibits distinct proteomic alterations, particularly ribosome and CCC pathway dysregulation. and are potential biomarkers for HIV-CRC.
Discovery of Seven ROS-Sensitive Immune Checkpoints and 46 Ligands Mediating Immune Suppression Through T cell-APC Networks.
Han B, Xu K, Saaoud F … +7 more , Hou Y, Shao Y, Lu Y, Jiang X, Zhao H, Wang H, Yang X
J Cancer · 2026 · PMID 41584046 · Full text
The functional landscape of immune checkpoints (ICs) operating on CD4⁺FoxP3⁺ regulatory T cells (Tregs) remain incompletely defined. Although canonical IC pathways are well characterized, the full spectrum of IC molecule...
The functional landscape of immune checkpoints (ICs) operating on CD4⁺FoxP3⁺ regulatory T cells (Tregs) remain incompletely defined. Although canonical IC pathways are well characterized, the full spectrum of IC molecules governing Treg-mediated immune regulation across physiological and pathological contexts has not been fully explored. We performed a comprehensive, multi-dataset transcriptomic screening of Treg membrane proteins to identify candidate immune checkpoints. This approach yielded 151 putative novel ICs, including 45 Treg-specific molecules and 106 FoxP3⁺-upregulated candidates. Cross-referencing these candidates with ten well-established IC-deficient models refined the list to 85 high-confidence ICs. A subsequent high-stringency, integrating expression specificity, functional relevance, and cross-dataset consistency, was applied to identify seven the most robust candidates. Ligand-receptor interaction mapping was then performed to define associated IC ligands and characterize their cellular expression patterns. This integrative analysis identified seven previously unrecognized immune checkpoints: CEP55, CD38, EHD4, CD200R1, PRC1, RAPH1, and CD86 expressed across Tregs and multiple T cell subsets. Ligand interaction mapping further revealed 46 corresponding IC ligands, predominantly expressed on antigen-presenting cells and tumor cells. Together, these IC-ligand interactions form extensive regulatory networks that modulate immune signaling and inflammatory responses. Our study delineates a comprehensive immune checkpoint-ligand network encompassing seven novel ICs and 46 associated ligands, providing mechanistic insight into Treg- and T cell-mediated immune regulation. This expanded IC landscape broadens the current repertoire of immune modulatory pathways and highlights new therapeutic opportunities across cancer, autoimmune disorders, infectious diseases, transplantation immunology, inflammatory conditions, and cardiovascular diseases.
Neoadjuvant Pembrolizumab Combined with Chemotherapy for Locally Advanced Resectable Oral and Oropharyngeal Squamous Cell Carcinomas: A Single-center Retrospective Study.
Geng X, Zhao Y, Wu Y … +4 more , Ma X, Xia R, Xu X, Ren G
J Cancer · 2026 · PMID 41584045 · Full text
Neoadjuvant chemotherapy regimens have shown encouraging efficacy characterized by high objective response rate (ORR), pathologic complete response (pCR) rate, and major pathologic response (MPR) rate, alongside acceptab...
Neoadjuvant chemotherapy regimens have shown encouraging efficacy characterized by high objective response rate (ORR), pathologic complete response (pCR) rate, and major pathologic response (MPR) rate, alongside acceptable safety. This single-center retrospective study aimed to evaluate the safety and efficacy of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced resectable oral and oropharyngeal squamous cell carcinomas (LA-OSCC/OPSCC). A total of 50 patients were included. The patients received 2-4 cycles of neoadjuvant therapy with pembrolizumab, albumin-bound paclitaxel and cisplatin before surgery, followed by adjuvant radiotherapy or immunotherapy. The median follow-up time was 31.7 months (95%CI, 29.4-34.0). The ORR was 85.4%, and the MPR rate was 65.8%. The 1-year event-free survival (EFS) rate was 88.8% (95%CI, 79.8%-98.8%). Patients with moderate programmed cell death ligand 1 (PD-L1) expression (combined positive score (CPS) 1 to <10) achieved the highest MPR rate (71.4%), underscoring the potential predictive value of PD-L1 expression. Treatment-related adverse events (TRAEs), most commonly alopecia, anemia, neutropenia, and nausea, were manageable. No treatment-related deaths occurred. This retrospective analysis indicates that neoadjuvant pembrolizumab combined with chemotherapy is a promising strategy for patients with LA-OSCC/OPSCC. Future prospective studies with larger cohorts and longer follow-up are warranted to confirm these findings.
Identification of super-enhancer-based biomarkers for predicting survival and immunotherapy efficacy in colorectal cancer.
Yu Y, Zhang X, Ma X … +6 more , Ren J, Zhang J, Zhu L, Chen Y, Lu Z, Li J
J Cancer · 2026 · PMID 41584044 · Full text
Immune checkpoint inhibitors are effective treatments for many tumors. However, existing biomarkers can benefit only a small selection of colorectal cancer patients. Super-enhancers are associated with various tumor char...
Immune checkpoint inhibitors are effective treatments for many tumors. However, existing biomarkers can benefit only a small selection of colorectal cancer patients. Super-enhancers are associated with various tumor characteristics. We wondered whether super-enhancer-related genes could be novel biomarkers for immunotherapy. We screened super-enhancer-related genes that were highly correlated with immune infiltration through weighted gene co-expression network analysis on the basis of chromatin immunoprecipitation sequencing data. A prognostic risk signature was established using least absolute shrinkage and selection operator and cox regression models. By analyzing the correlations between the expression of model genes and the immunophenotypic and microsatellite instability scores, we determined that and expression had high predictive value for immunotherapy efficacy. Moreover, we predicted the sensitivity of the PLAU and GSDMC proteins to drugs by virtual docking. Finally, we validated the effect of the super-enhancer activity on and expression. Overall, our study identified super-enhancer-based biomarkers for predicting survival and immunotherapy efficacy in colorectal cancer.
Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway.
Kuang S, Feng W, He S … +3 more , Meng W, Yang C, Ning Y
J Cancer · 2026 · PMID 41584043 · Full text
6RK73 is a novel drug designed to target UCHL1 deubiquitinase. Preliminary studies have indicated its anti-cancer activity in breast cancer and renal cell carcinoma. However, its potential anti-cancer effects in other ma...
6RK73 is a novel drug designed to target UCHL1 deubiquitinase. Preliminary studies have indicated its anti-cancer activity in breast cancer and renal cell carcinoma. However, its potential anti-cancer effects in other malignancies, including ovarian cancer, remain unclear. In this study, we first determined the IC50 values of 6RK73 in ovarian cancer cell lines OVCAR3 and SKOV3, which were 10.62 μM and 12.90 μM, respectively. Subsequently, we found that 6RK73 effectively inhibited cell proliferation and arrested cell cycle progression in ovarian cancer cells . Furthermore, 6RK73 suppressed the formation of subcutaneous ovarian cancer tumors in nude mice. Mechanistically, 6RK73 significantly inhibited the AKT1/Sp1/c-Myc signaling pathway, which not only disrupted the interaction between Sp1 and c-Myc but also reduced Sp1 deubiquitination, thereby downregulating c-Myc protein expression. Interestingly, the anti-tumor effects of 6RK73 in ovarian cancer were independent of UCHL1 inhibition. Finally, AKT1 overexpression reversed the 6RK73-mediated suppression of cell proliferation by reactivating the AKT1/Sp1/c-Myc signaling pathway. These findings suggest that 6RK73 is a promising anti-cancer agent that exerts its effects by inactivating AKT1/Sp1/c-Myc signaling in ovarian cancer.
Hypoxia-Driven Immune Escape in Clear Cell Renal Cell Carcinoma: A Prognostic Model and Dual-Functional Biomarker PLOD2 for Immunotherapy Stratification.
Xiao F, Guan Y, Song H … +1 more , Xiang W
J Cancer · 2026 · PMID 41584042 · Full text
For patients with recurrent or metastatic clear cell renal cell carcinoma (ccRCC), immunotherapy has demonstrated substantial antitumor activity. However, accurately predicting which patients will benefit from these ther...
For patients with recurrent or metastatic clear cell renal cell carcinoma (ccRCC), immunotherapy has demonstrated substantial antitumor activity. However, accurately predicting which patients will benefit from these therapies remains a major challenge. This study aims to elucidate the regulatory role of the hypoxic tumor microenvironment in immune suppression and immune escape, to develop a hypoxia-based prognostic model, and to identify key biomarkers to guide personalized treatment decisions. We applied weighted gene co-expression network analysis (WGCNA) to screen hypoxia-related genes and constructed a hypoxia risk score (HRS) model using LASSO-Cox regression. We found that the HRS model effectively predicted immunotherapy response and prognosis, with patients in the high-HRS group exhibiting significantly shorter overall survival. A high HRS was associated with immune escape by reshaping the T-cell-infiltrated tumor microenvironment (TME), and showed strong positive correlations with cancer-immunity cycle activity, PD-L1/CTLA-4 immune checkpoint expression, and T-cell inflammation scores. Importantly, cell-based and animal experiments demonstrated that PLOD2, a key gene in the HRS model, plays a critical role in hypoxia-induced immune escape in ccRCC. PLOD2 significantly promoted ccRCC cell growth and migration and . High PLOD2 expression in clinical samples was associated with ccRCC progression and potentially enhanced sensitivity to immunotherapy by modulating tumor mutational burden and immune escape-related pathways. In summary, our study successfully constructed an HRS model to predict the efficacy of immune checkpoint inhibitor (ICI)-based immunotherapy. PLOD2 was identified as a dual-functional biomarker with both prognostic and predictive value for immunotherapy. The HRS model provides a quantitative tool for immunotherapy stratification. Notably, high PLOD2 expression indicates tumor progression yet paradoxically associates with enhanced immunotherapy response through activation of immune escape pathways, thereby offering a potential therapeutic target for converting "cold tumors" into "hot tumors".
Talin1 Mediates Tumor-Nerve Interactions in Prostate and Breast Cancer Cells.
Hwang BJ, Polanco G, Sane S … +5 more , Almeida IC, Tsuzaka K, Denaro F, Rezvani K, Odero-Marah VA
J Cancer · 2026 · PMID 41584041 · Full text
Prostate cancer (PCa) and breast cancer (BCa) are the leading causes of death in men and women in the US. Neurite outgrowth is a fundamental process in differentiating neurons and contributes to cancer progression. Snail...
Prostate cancer (PCa) and breast cancer (BCa) are the leading causes of death in men and women in the US. Neurite outgrowth is a fundamental process in differentiating neurons and contributes to cancer progression. Snail transcription factor promotes cancer progression and regulates neurite outgrowth in PCa cells, but their molecular mechanisms are not fully understood. We hypothesize that Snail can stimulate neurite outgrowth through the secretion of extracellular vesicles. To test this hypothesis, we isolated exosomes from PCa (C4-2 non-silencing (NS) control and C4-2 Snail knockdown) and BCa (MCF7 Neo control and MCF7 Snail overexpressing) cells, which were confirmed by western blot analysis and Transmission Electron Microscopy. Proteomics of isolated exosomes from Snail-expressing C4-2 cancer cells shows predominantly Talin1 proteolyzed C-terminal rod domain and N-terminal head domain within exosomes, while full-length Talin1 is found in whole cell lysates. A significantly higher percentage of NPC (Neural Progenitor Cells) with neurite outgrowth is observed when cultured with conditioned medium or exosomes collected from C4-2 NS PCa or MCF7 Snail BCa cells expressing high levels of Snail compared to C4-2 Snail knockdown or MCF7 Neo, respectively. A similar trend is observed for increased average neurite length due to Snail expression. Furthermore, we find that mH, a specific inhibitor of proteolyzed Talin1, reduces Snail-induced neurite outgrowth and AKT activation within neurons. Overall, Snail may promote cancer-nerve interactions Talin1, indicating that Talin1 inhibitors can be a potent targeted therapy in malignant tumors with neurite outgrowth.
Spatial Profiling and Prognostic Role of Tumor-Infiltrating CD8+ T and CD20+ B Cells in Metastatic Clear Cell Renal Cell Carcinoma Treated with Sequential Tyrosine Kinase Inhibitors and Nivolumab.
Trailin A, Červenková L, Hošek P … +5 more , Pivovarčíková K, Tkadlecová M, Stránský P, Hemminki K, Fiala O
J Cancer · 2026 · PMID 41584040 · Full text
: Tumor-infiltrating lymphocytes (TILs) are known to influence disease progression and treatment response in clear cell renal cell carcinoma. This study aimed at evaluating the prognostic and predictive relevance of T an...
: Tumor-infiltrating lymphocytes (TILs) are known to influence disease progression and treatment response in clear cell renal cell carcinoma. This study aimed at evaluating the prognostic and predictive relevance of T and B cell infiltration patterns in patients with metastatic clear cell renal cell carcinoma (mRCC-cc) treated sequentially with tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitor nivolumab. : In this retrospective cohort study, immune cell densities (CD3+, CD8+ T cells and CD20+ B cells) were analyzed by immunohistochemistry and quantified using digital image analysis software QuPath in distinct tumor regions of primary tumor: tumor center (TC), inner margin (IM), outer margin (OM), and peritumoral (PT) region. Samples were obtained from 36 patients with mRCC-cc treated with TKIs in the first line and sequentially with nivolumab in the second or third-line setting. Associations between immune cell densities, clinicopathological features, and survival outcomes were assessed using univariable and multivariable Cox regression models. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. : Densities of all immune cells were significantly higher in the OM and PT regions than in the TC and IM. Older age correlated with lower CD8+ T cell and CD20+ B cell densities, whereas higher tumor grade was associated with increased CD20+ B cell infiltration in IM. High CD20+ B cell density in IM and OM was significantly associated with shorter PFS during first-line TKI therapy (hazard ratio (HR) = 3.30, P = 0.015 and HR = 3.25, P = 0.016, respectively). In contrast, an intermediate CD8+ T cell density in the PT region was associated with longer PFS during sequential nivolumab treatment (HR = 0.26, P = 0.007). No significant associations between immune cell densities and ORR or OS were observed. : Our findings suggest that spatial localization and density of tumor-infiltrating CD20+ B cells are potential predictors of poor PFS on TKIs, whereas higher CD8+ T cell infiltration in peritumoral areas may be a potential predictor of prolonged PFS on nivolumab. These immune-cell-based parameters may refine prognostic models and help guide treatment selection in mRCC-cc.
In-depth Biological Monitoring to Estimate Effects of Red or Processed Meat on Colorectal Cancer.
Lee JS, Kim E, Lee UJ … +4 more , Lee MA, Um AS, Lee HS, Yang M
J Cancer · 2026 · PMID 41584039 · Full text
: The intake of red or processed meat remains controversial as a crucial factor for CRC. Thus, we performed in-depth biological monitoring. We performed a case- control study and analyzed various exposure and response b...
: The intake of red or processed meat remains controversial as a crucial factor for CRC. Thus, we performed in-depth biological monitoring. We performed a case- control study and analyzed various exposure and response biomarkers including 1-OHP, MeIQx, and PhIP, and malondialdehyde (MDA), and heterocyclic amine (HCA)-DNA adducts in Korean cases and controls (N = 218). They consumed 53.4 ± 74.0 g/day of red meat and 1.1 ± 3.7 g/day of processed meat. The CRC presence was associated with sex, BMI, tobacco smoking, alcohol drinking, cooking method of meat, and vegetable consumption, rather than red or processed meat intake. The levels of MDA were positively associated with those of 1-OHP, MeIQx, or PhIP. The sum of 1-OHP, MeIQx, and PhIP was associated with the levels of HCA-DNA adducts and cooking method of meat. In addition, the above biomarkers for CRC were associated with each other. However, most of these biomarkers were not higher in CRC patients than those in controls. The present in-depth biological monitoring provides that red or processed meat may induce oxidative stress; however, present intake of the meat and the intake-related oxidative stress may not affect CRC prevalence among the Korean population, who consume less meat than Westerners.
Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.
Lei Y, Peng L, Qin Z … +9 more , Luo J, Luo Y, Fan Z, Wang J, Huang S, Zhao H, Lin S, Xiang L, Luo Y
J Cancer · 2026 · PMID 41584038 · Full text
Gastrointestinal tumors are among the most common tumors worldwide and are currently the leading cause of cancer-related deaths. Gastrointestinal tumors affect the digestive system and include esophageal, liver, gastric,...
Gastrointestinal tumors are among the most common tumors worldwide and are currently the leading cause of cancer-related deaths. Gastrointestinal tumors affect the digestive system and include esophageal, liver, gastric, colorectal, and pancreatic cancers. Aerobic glycolysis is a widespread phenomenon among gastrointestinal tumor cells, which poses a major hazard to human health and life. Increasing evidence suggests that aerobic glycolysis can induce and promote the development of gastrointestinal tumors by rapidly providing large amounts of energy and altering the tumor microenvironment. Among them, glucose transporter proteins and key enzymes involved in glycolysis are expressed at higher levels during aerobic glycolysis, and the corresponding signaling pathways and transcription regulatory factors are activated, playing an important role in the occurrence and development of tumors. Additionally, evidence has indicated that aerobic glycolysis plays an essential role in inhibiting the development of immune cells, modifying the population of immune cells present in the surrounding tumor, and promoting the polarization of immune cells. Moreover, drugs and compounds that target essential enzymes and transcription factors associated with glycolysis are known to exhibit anticancer properties.
Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.
Ke TL, Chen L
J Cancer · 2026 · PMID 41584037 · Full text
Rhabdomyosarcoma (RMS) is a rare disease that arises from skeletal muscle mainly affects children and adolescents. Patients with RMS have diverse symptoms and prognosis based on tumor sizes, tumor anatomical locations, h...
Rhabdomyosarcoma (RMS) is a rare disease that arises from skeletal muscle mainly affects children and adolescents. Patients with RMS have diverse symptoms and prognosis based on tumor sizes, tumor anatomical locations, histological subtypes of the tumors and genetic testing of () fusion gene. The 4 subtypes of RMS include embryonal RMS (eRMS), alveolar RMS (aRMS), spindle cell/sclerosing RMS (scRMS) and pleomorphic RMS (pRMS). Treatment for RMS patients remains challenging due to its heterogeneous nature. Thus, a combinatory approach is likely to warrant better management of RMS. Given that fusion gene is the most common biomarker for RMS, though this fusion gene only accounts for 16-20% of RMS patients. Targeted therapy that tailors treatment plans to the individual patient may provide additional benefits for RMS patients. This review describes the frequent genetic mutations observed in RMS patients and drug development based on these mutations shall provide direction to develop targeted therapy leading to effective personalized treatment for RMS patients.
Dysregulation of SRSF11 in Cancer: Mechanistic Insights and Biomarker Potential for Diagnosis and Therapy.
Jun Y, Shanshan L, Jingwen X … +3 more , Yu H, Jianlong X, Qingfeng S
J Cancer · 2026 · PMID 41584036 · Full text
Serine/arginine-rich splicing factor 11 (SRSF11) is an RNA-binding regulator that modulates alternative splicing and RNA metabolism in a context-dependent manner across selected malignancies. Evidence from colorectal, he...
Serine/arginine-rich splicing factor 11 (SRSF11) is an RNA-binding regulator that modulates alternative splicing and RNA metabolism in a context-dependent manner across selected malignancies. Evidence from colorectal, hepatocellular, gastric, glioma, and a few other cancers indicates that SRSF11 participates in cell-cycle regulation, telomerase recruitment, and epithelial-mesenchymal transition (EMT) through specific signaling axes, including PAK5-SRSF11-HSPA12A in colorectal cancer, METTL3-SRSF11 in gastric and breast cancers, and SRSF11-CDK1/telomerase circuits in hepatocellular carcinoma. These mechanisms highlight SRSF11 as a candidate biomarker for diagnosis and prognosis rather than a universal oncogenic driver. We summarize the current mechanistic, post-translational, and non-coding RNA-mediated regulatory evidence, clarify the limitations of existing data, and propose future multi-omics and functional approaches to validate SRSF11-directed splicing therapy. This review integrates mechanistic insight with clinical evidence while emphasizing cancer-specific rather than generalized conclusions.
Sialylation in Thyroid Carcinoma: An Overview of Mechanisms, Markers, and Therapeutic Opportunities.
Li C, Zhou J, Zhang L … +3 more , Si Y, Zhang X, Shen M
J Cancer · 2026 · PMID 41584035 · Full text
Thyroid carcinoma (TC) is the most prevalent malignancy of the endocrine system, with its incidence rising annually worldwide. Post-translational modifications and epigenetic changes have been documented to be pivotal in...
Thyroid carcinoma (TC) is the most prevalent malignancy of the endocrine system, with its incidence rising annually worldwide. Post-translational modifications and epigenetic changes have been documented to be pivotal in the initiation, progression, and malignant transformation of TC. In addition to mediating biological processes such as cell recognition, signal transduction, and immune regulation, these modifications can also significantly impact the development and metastasis of various cancers. Among these, sialylation is identified as a key post-translational modification, showing close associations with the invasiveness and metastatic potential of TC. This review aims to provide an overview of the current understanding of sialylation in TC, highlighting its underlying mechanisms and examining its roles in cell proliferation, invasion, and immune evasion. Additionally, this study intends to explore the potential of targeting sialylation as a novel therapeutic approach, providing new perspectives for TC prevention and treatment, as well as the development of new therapeutic agents.
Roles of AFP, AFP-L3, DCP and GP73 in Diagnosis of Hepatocellular Carcinoma and Prediction of Recurrence in Patients.
Liao Y, Mo Z, Ye C … +3 more , Chen Y, Dong H, Hu B
J Cancer · 2026 · PMID 41584034 · Full text
Alpha-fetoprotein (AFP), Des-gamma carboxy-prothrombin (DCP), lectin-bound AFP (AFP-L3) and Golgi protein-73 (GP73) have been used or proposed as surveillance tests for hepatocellular carcinoma (HCC). The aims of this st...
Alpha-fetoprotein (AFP), Des-gamma carboxy-prothrombin (DCP), lectin-bound AFP (AFP-L3) and Golgi protein-73 (GP73) have been used or proposed as surveillance tests for hepatocellular carcinoma (HCC). The aims of this study were to determine the performance of AFP, DCP, AFP-L3, GP73 and their combination in the diagnosis and prognosis of HCC. A total of 578 patients were enrolled, including 303 HCC patients, 104 patients with liver cirrhosis, 101 patients with chronic hepatitis and 70 healthy volunteers. The serum levels of AFP, DCP, AFP-L3 and GP73 were quantified before treatment, 7 days and 30 days after treatment. AFP had the best area under the curve (AUC = 0.850), followed by DCP (0.775) and AFP-L3 (0.763), for the prediction of HCC, whereas GP73 had low diagnostic value (0.549). The combination of AFP, DCP and AFP-L3 significantly improved diagnostic performance (AUC = 0.895). The level of AFP 30 days after treatment had the best predictive value for HCC recurrence (AUC = 0.779). Higher recurrence rates were associated with an increasing number of elevated tumor markers measured both before and 30 days after treatment. Furthermore, patients whose marker status remained positive 30 days after treatment had a higher recurrence rate than patients whose marker status changed to negative. AFP was more effective than DCP and AFP-L3 for the diagnosis and prognosis of HCC, and the combination of AFP, AFP-L3 and DCP enhanced the diagnostic performance. The dynamic changes in biomarker positive status after treatment and the number of positive biomarkers play important roles in predicting HCC recurrence.
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