Oncology Letters最新文献

{"title":"Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with vascular invasion: A systematic review and meta-analysis.","authors":"Yuhao Su, Yuxin Liang, Deyuan Zhong, Hongtao Yan, Qinyan Yang, Xiaolun Huang","doi":"10.3892/ol.2026.15619","DOIUrl":"10.3892/ol.2026.15619","url":null,"abstract":"<p><p>Advances in conformal and image-guided external-beam radiotherapy have expanded its application in hepatocellular carcinoma (HCC); however, the benefit of neoadjuvant radiotherapy before resection for HCC with vascular invasion remains uncertain. A systematic review and meta-analysis were conducted comparing neoadjuvant radiotherapy plus hepatectomy vs. hepatectomy alone in resectable HCC with vascular invasion. Databases were searched through August 1, 2024. Primary outcomes were overall survival (OS) and disease-free survival (DFS). A total of four studies (n=362) were included. In the overall pooled analysis, neoadjuvant radiotherapy was not associated with a statistically significant improvement in 1-year OS [risk ratio (RR) 1.62; 95% confidence interval (CI) 0.71-3.69] or 2-year OS (RR 2.64; 95% CI 0.57-12.27), with considerable heterogeneity (I² 97 and 94%, respectively). Similarly, 1-year DFS was not significantly different between groups (RR 2.68; 95% CI 0.50-14.43; I² 95%). In subgroup analyses by vascular invasion type, patients with portal vein tumor thrombus (PVTT) showed a higher 1-year and 2-year OS compared with surgery alone, and two studies reporting time-to-event outcomes suggested lower recurrence and mortality; however, these findings are based on a small number of studies and should be interpreted with caution. Reported radiotherapy-related toxicities were generally manageable. Overall, current evidence is limited and heterogeneous; neoadjuvant radiotherapy may benefit selected patients with resectable HCC and PVTT, but adequately powered multicenter randomized trials with standardized protocols are needed.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"264"},"PeriodicalIF":2.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early postoperative complications and patient-reported quality of life following breast-conserving surgery with intraoperative radiotherapy: A prospective cohort study.","authors":"Hongmei Han, Xuwen Liu, Baozhong Zhang, Jingjing Liu, Jing Wang, Qingsong Pang","doi":"10.3892/ol.2026.15623","DOIUrl":"10.3892/ol.2026.15623","url":null,"abstract":"<p><p>The present study aimed to evaluate the incidence of short-term complications and health-related quality of life (HRQoL) in patients with breast cancer undergoing breast-conserving surgery (BCS) with intraoperative radiotherapy (IORT), and to identify associated influencing factors. The study prospectively analyzed clinical data from women who underwent BCS with IORT at Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between March 2021 and June 2023. Telephone follow-up was conducted within 3 months post-surgery to assess surgery- and radiotherapy-related complications. HRQoL was evaluated using the BREAST-Q BCS module and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Statistical analyses were performed using SPSS 27.0. Among 102 enrolled patients, common complications included incision site sclerosis (84.3%), pain (58.8%) and skin indentation (44.1%). Severe complications such as infection (7.8%) and delayed healing (12.7%) were less frequent. Grade I-II acute radiation dermatitis occurred in 73.5% of patients. Univariate analysis revealed that larger applicator size was significantly associated with higher-grade skin toxicity, skin indentation and irritation (P<0.01). Older age was a risk factor for incision infection and delayed healing (P<0.05). Larger tumor size (T stage) adversely affected satisfaction with breasts and chest physical well-being scores (P<0.01). The study concluded that, in patients with early-stage breast cancer treated with BCS plus IORT, 3-month postoperative complications are predominantly mild localized tissue reactions with rare severe events. Applicator size, age and tumor stage are significantly associated with early complications and acute-phase QoL, informing preoperative counseling and perioperative management optimization. However, this study only reflects acute recovery outcomes; long-term follow-up of the cohort is ongoing to evaluate late toxicities, cosmetic results and sustained QoL.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"268"},"PeriodicalIF":2.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational discovery of novel colony-stimulating factor-1 receptor as a potential therapeutic biomarker in osteosarcoma and a novel inhibitor from herbal sources.","authors":"Hui Zhang, Shiwei Wu, Dan Luo, Jincai Guo","doi":"10.3892/ol.2026.15618","DOIUrl":"10.3892/ol.2026.15618","url":null,"abstract":"<p><p>Osteoclast differentiation and activation pathways drive abnormally enhanced bone resorption in osteosarcoma, and have thus emerged as potential therapeutic targets for this malignancy. However, the diagnostic value of osteoclast differentiation-related genes (ODRGs) in osteosarcoma remains largely uncharacterized. The present study first analyzed the expression profiles of ODRGs in osteosarcoma using multiple Gene Expression Omnibus datasets. Analysis of single cell RNA-sequencing data from osteosarcoma tissues demonstrated that colony-stimulating factor-1 receptor (CSF1R), a key ODRG, was widely expressed in osteoblasts and monocyte/macrophage lineages within the osteosarcoma microenvironment. Subgroup analysis further revealed that patients with osteosarcoma in the low-CSF1R expression group exhibited significantly increased sensitivity to immune checkpoint inhibitors compared with those in the high-CSF1R expression group. Furthermore, pan-cancer analysis across The Cancer Genome Atlas datasets demonstrated that CSF1R expression was aberrantly regulated in multiple tumor types and strongly correlated with the expression levels of immune checkpoint markers and the infiltration levels of immune cells. Functional validation experiments confirmed that treatment with CSF1R-specific inhibitors significantly reduced the viability of the MG63 and Saos-2 cell lines. To identify novel, natural-product-derived CSF1R inhibitors, structure-based virtual screening was combined with in vitro experimental assays (CCK-8 and western blotting). Among the validated candidates, sarsasapogenin, a compound identified from the screen, effectively suppressed CSF1R protein expression and inhibited the proliferation of both MG63 and Saos-2 cells in a dose-dependent manner. Collectively, the present findings highlight CSF1R as a clinically promising diagnostic biomarker and therapeutic target for osteosarcoma.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"263"},"PeriodicalIF":2.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis.","authors":"Christoph Schaefers, Annika Poch, Anika Forstreuter, Frederike Bokemeyer, Carsten Bokemeyer, Christoph Seidel","doi":"10.3892/ol.2026.15616","DOIUrl":"10.3892/ol.2026.15616","url":null,"abstract":"<p><p>Smoking may influence cancer treatment outcomes; however, there is conflicting evidence on the efficacy of immune checkpoint inhibitors (ICIs) in active smokers. It has been suggested that smokers receiving ICIs may achieve improved outcomes compared with non-smokers. The present study aimed to challenge this assumption by investigating the prognostic impact of smoking status and other characteristics in patients with metastatic or advanced cancer undergoing ICI therapy. In the present study, patients with predetermined solid tumors who received ICIs either as a monotherapy or in combination regimens in a palliative treatment setting were retrospectively evaluated. Patients were included if they had received >1 dose of an ICI and had an available smoking status. Kaplan-Meier estimates were used to analyze the associations between smoking status and overall survival (OS) and progression-free survival (PFS). The patient baseline characteristics were assessed as potential prognostic markers using univariate and multivariate analyses. Of the 464 patients evaluated, 180 met the inclusion criteria. The cohort included patients with lung cancer (n=94), renal cell carcinoma (n=18), urothelial cancer (n=21), melanoma (n=3), and head and neck cancer (n=44). The median OS and PFS times for the whole cohort were 39.1 and 5.5 months, respectively. Patients were categorized as never-smokers (n=45, 25%), former smokers (n=81, 45%) and active smokers (n=54, 30%). The median OS times for the never, former and active smokers were 66.4, 31.6 and 13.9 months, respectively. When comparing the active smokers with the former and never smokers, the median OS times were 13.9 vs. 41.1 months (P=0.069, trend). Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) performance status ≥3 [hazard ratio (HR), 5.85; P=0.002], neutrophil-to-lymphocyte ratio (NLR; HR, 1.11; P=0.017), lactate dehydrogenase (LDH; HR, 1.00; P<0.001) and C-reactive protein (CRP) levels as continuous variables (HR, 1.01; P=0.002) as significant predictors of a poorer OS. For PFS, multivariate analysis identified sex (HR, 0.69; P=0.049), age (HR, 0.98; P=0.014) and ECOG performance status ≥3 (HR, 5.83; P<0.001) as independent predictors of a shorter PFS. In conclusion, contrary to prior hypotheses suggesting improved outcomes for smokers undergoing ICI therapy, the results of the present study demonstrated a trend towards impaired survival outcomes in active smokers compared with never and former smokers. The independent prognostic factors for a poorer OS included a poor ECOG performance status, CRP level, LDH level and NLR.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"261"},"PeriodicalIF":2.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta-analysis.","authors":"Javier Angel Canelas Fernández, Jéssica Alonso-Molero, Paz Rodríguez-Cundín, Javier Llorca, Inés Gómez-Acebo, Trinidad Dierssen-Sotos","doi":"10.3892/ol.2026.15617","DOIUrl":"10.3892/ol.2026.15617","url":null,"abstract":"<p><p>Breast cancer is a global health concern. Hormone replacement therapy (HRT) prior to breast cancer diagnosis is of particular interest due to the hormone sensitivity of the breasts. Previous evidence has altered the perception of HRT by highlighting that certain risks could outweigh the benefits. As a result, the popularity of HRT for menopausal symptom relief and disease prevention decreased. To investigate the relationship between pre-diagnosis HRT use and breast cancer survival, a meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search across MEDLINE, Cochrane and Web of Science databases up to August 2025 identified 33 studies. These studies evaluated the impact of HRT on breast cancer survival utilizing various study designs. Quality assessment was performed using the Newcastle Ottawa Scale, while the Risk of Bias in Non-Randomized Studies of Exposures tool was used to evaluate the risk of bias. The pooled analysis revealed that HRT use prior to breast cancer diagnosis was associated with reduced breast cancer mortality (odds ratio, 0.86; 95% CI, 0.79-0.94). Subgroup analyses based on duration and timing of HRT use at diagnosis revealed heterogeneous associations with survival. Shorter duration of use (<5 years) appeared to be associated with lower breast cancer mortality; however, these subgroup analyses were based on a limited number of studies and should be interpreted with caution. Longer duration of use (>10 years) showed no clear association. Studies recruiting after 2000 showed an inverse association between HRT use and breast cancer mortality, a trend more pronounced than in earlier years, although evidence remains limited. In conclusion, pre-diagnosis HRT use was associated with improved breast cancer survival, influenced by treatment duration, timing and temporal factors. It is necessary to note that subgroup findings based on the treatment duration and recruitment period were limited by the low number of contributing studies and should be interpreted with caution. Despite methodological differences among the included studies, the present findings provide valuable insights into the complex relationship between HRT and breast cancer prognosis.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"262"},"PeriodicalIF":2.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual roles of neutrophil extracellular traps in tumors: From pro-metastatic mechanisms to immunotherapeutic strategies (Review).","authors":"Mingxin Guo, Han Wang, Jiaqi Zeng, Ning Wu, Zhiqiang Hu, Ao Xue, Ting Dai","doi":"10.3892/ol.2026.15614","DOIUrl":"10.3892/ol.2026.15614","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) serve a dual role in tumor progression. On the one hand, they promote tumor invasion and metastasis by facilitating cancer cell adhesion to the endothelium, supporting vascular remodeling and establishing pre-metastatic niches. On the other hand, NETs exert potent immunosuppressive effects that foster tumor immune evasion and contribute to immunotherapy resistance. Specifically, NETs create physical barriers within the tumor microenvironment, directly suppress effector immune cells, and degrade critical molecules such as interferon-γ, leading to immune exhaustion and dysfunction. The present review comprehensively summarizes the biology of NETs and their molecular mechanisms in tumor metastasis, with a particular focus on NET-mediated immunosuppression and its causal link to immunotherapy resistance. This review further discusses emerging strategies that disrupt NET formation or function, which may reverse their immunosuppressive impact and restore antitumor immunity, thereby enhancing the efficacy of current immunotherapies.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"259"},"PeriodicalIF":2.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging role of protein arginine methyltransferase 5 in gastrointestinal cancer (Review).","authors":"Rui Zhang, Yiwen Lu, Xiaohua Fang, Fengquan Zhang, Weidong Wu, Jie Song, Zhenzhen Liang","doi":"10.3892/ol.2026.15613","DOIUrl":"10.3892/ol.2026.15613","url":null,"abstract":"<p><p>Gastrointestinal (GI) cancer remains a leading cause of cancer-related mortality worldwide, with epigenetic alterations progressively recognized as key drivers of tumorigenesis and therapeutic resistance. Through its role in facilitating cell proliferation, inhibiting apoptosis, driving epithelial-mesenchymal transition (EMT) and metastasis, reinforcing angiogenesis, inducing metabolic reprogramming, mediating chemoradiotherapy resistance and maintaining cancer stem cell (CSC) properties, protein arginine methyltransferase 5 (PRMT5) has emerged as a key oncogenic regulator among these epigenetic modifiers implicated in GI cancer progression. Elevated PRMT5 expression has been observed in multiple GI cancer subtypes, comprising gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer, where PRMT5 markedly contributes to tumorigenesis via symmetric dimethylation of histone (e.g., dimethylation of histone H4 at arginine 3) and non-histone substrates [e.g., AKT1 and sterol regulatory element-binding protein 1a (SREBP1a)]. In GC, PRMT5 activates the PI3K/AKT pathway [e.g., by methylating AKT1 at arginine (R)391 and upregulating c-Myc], facilitating tumor cell proliferation and survival. In CRC, PRMT5-mediated methylation of SMAD4 (e.g., at R361) reinforces TGF-β signaling, facilitating EMT and metastasis, while its interaction with EGFR further amplifies proliferative signals. PRMT5 also upregulates VEGF expression (e.g., via chromatin remodeling at its promoter), stimulating angiogenesis and inhibits ferroptosis (e.g., by suppressing the solute carrier family 7 member 11/glutathione peroxidase 4 axis in HCC), supporting tumor survival. Furthermore, PRMT5 markedly contributes to metabolic reprogramming (e.g., accelerating <i>de novo</i> lipogenesis via SREBP1a methylation and glycolysis via epigenetic silencing of F-box and WD repeat domain-containing protein 7), while strengthening DNA repair (e.g., homologous recombination) and CSC self-renewal (e.g., via the β-catenin/IL-8 axis in CRC) to confer therapy resistance. However, PRMT5 inhibitors (e.g., GSK3326595 and JNJ-64619178) demonstrate antitumor effects in preclinical models and methylthioadenosine phosphorylase (MTAP) deletion may serve as a potential biomarker for patient selection. The clinical translation of PRMT5 inhibitors is limited by hematological toxicity, lack of robust predictive biomarkers beyond MTAP and potential resistance from compensatory PRMT family members. It is key to clarify GI cancer-specific PRMT5 mechanisms and potentially develop optimized combination therapies in the future.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"258"},"PeriodicalIF":2.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant immunotherapy plus chemotherapy and maintenance immunotherapy for pulmonary lymphoepithelioma-like carcinoma with hepatitis B virus infection, KRAS mutation and high expression of programmed death ligand 1: A case report.","authors":"Jing Zhu, Qing-Gui Xu, Jiao Zhu, Rui-Xiang Zhou, Yu-Chuan Zhou, Zhi-Ke Li","doi":"10.3892/ol.2026.15612","DOIUrl":"10.3892/ol.2026.15612","url":null,"abstract":"<p><p>Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer, often associated with Epstein-Barr virus (EBV) infection. It typically exhibits distinct epidemiological and molecular features compared to other lung malignancies. However, the clinical behavior and optimal therapeutic strategies for PLELC, particularly in the presence of concomitant viral infections or specific genetic mutations, remain poorly defined. This report comprehensively outlines the treatment process of a 58-year-old female patient diagnosed with PLELC in the right middle lobe of the lung. Following surgical resection, the diagnosis was confirmed as PLELC, which was found to be associated with hepatitis B virus (HBV) infection, KRAS mutation and high expression of programmed death ligand 1 (PD-L1). The patient subsequently received adjuvant treatment with immunotherapy (penpulimab) combined with chemotherapy, followed by penpulimab maintenance therapy, resulting in a progression-free survival of >44 months. At present, the patient is still alive and healthy, and can undergo regular follow-ups and re-examinations. Notably, preoperative testing showed a positive EBV status, which became negative post-surgery. This case highlights several key aspects. First, it examines the diagnostic and therapeutic characteristics of PLELC with a positive EBV test result before surgery that turned negative after surgical resection. Second, it assesses the influence of high PD-L1 expression and concurrent HBV infection on the efficacy and safety of immunotherapy. Third, it explores the clinical implications of the KRAS mutation in this unique tumor subtype. The overarching goal of this exploration is to offer valuable clinical guidance for managing this rare and understudied subtype of lung cancer, particularly in the context of multimodal therapy involving immunotherapy.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"257"},"PeriodicalIF":2.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Interleukin-17 promotes the development of cisplatin resistance in colorectal cancer.","authors":"Guolong Sui, Yingna Qiu, Haijuan Yu, Qingbin Kong, Baowen Zhen","doi":"10.3892/ol.2026.15611","DOIUrl":"10.3892/ol.2026.15611","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3892/ol.2018.9645.].</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"256"},"PeriodicalIF":2.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An m6A-programmed cell death signature predicts prognosis and identifies STK25 as a therapeutic target in colon adenocarcinoma.","authors":"Hezhi Yu, Tihui Li, Xiaoyun Huang, Zihan Chen, Zixiang Lin, Fenglin Chen","doi":"10.3892/ol.2026.15610","DOIUrl":"10.3892/ol.2026.15610","url":null,"abstract":"<p><p>Colon adenocarcinoma (COAD) remains a leading cause of cancer-related mortality worldwide. Although programmed cell death (PCD) and RNA N6-methyladenosine (m6A) modification have each been shown to regulate tumor progression and therapeutic responses, their combined prognostic significance in COAD has not been fully elucidated. The present study aimed to develop an integrated m6A-PCD prognostic model and to identify potential therapeutic targets in COAD. In total, 1,379 genes across 14 PCD-related pathways were systematically analyzed and a 21-gene m6A-PCD signature (MCDI) was constructed following multivariate Cox regression analysis. Single-cell RNA sequencing from publicly available datasets (GSE132465 and GSE205506), together with reverse transcription-quantitative PCR (qPCR) validation using clinical samples, were employed to identify genes with tumor-specific expression patterns. The functional role of serine/threonine kinase 25 (STK25) was further investigated through knockdown experiments, flow cytometry, m6A methylated RNA immunoprecipitation (MeRIP)-qPCR and RIP assays. In addition, small interfering RNAs targeting methyltransferase-like 3 (METTL3) and YTH domain-containing protein 1 (YTHDC1) were used to evaluate the involvement of m6A modification in STK25 mRNA stability and apoptosis regulation. The resulting MCDI signature demonstrated robust and independent prognostic value and effectively predicted differential responses to programmed death-ligand 1 immunotherapy. In total, 5 core genes [microRNA 210, STK25, TGFB2, tripartite motif containing (TRIM)6 and TRIM68] were identified as key prognostic markers. STK25 was specifically upregulated in tumor epithelial cells, and its knockdown significantly promoted apoptosis in COAD cells. Correlation analyses revealed positive associations between STK25 expression and multiple m6A regulators, with METTL3 and YTHDC1 showing the highest targeting credibility. Knockdown of METTL3 or YTHDC1 reduced STK25 mRNA levels. RIP assays confirmed their direct binding to STK25 mRNA, while MeRIP-qPCR demonstrated that METTL3 knockdown decreased the m6A modification level of STK25 mRNA. In conclusion, the reconstructed MCDI was established as a novel m6A-PCD-based prognostic model for patient stratification and the prediction of immunotherapy response in patients with COAD. STK25 was also identified as a potential therapeutic target linking m6A modification to the regulation of apoptosis in COAD.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"31 6","pages":"255"},"PeriodicalIF":2.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}