Journal of Cancer最新文献

{"title":"Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.","authors":"Lixian Yang, Ke Wang, Wenjie Zeng, Yanwei Lu, Hailong Sheng, Hanchu Xiong, Haibo Zhang","doi":"10.7150/jca.132006","DOIUrl":"https://doi.org/10.7150/jca.132006","url":null,"abstract":"<p><p>Radiotherapy (RT) serves as a critical treatment modality for cancer, which not only destroys local tumor cells, but also exerts the \"double-edged sword\" impact on the immune system. While triggering anti-tumor immune response, RT also induces a great number of immunosuppressive cells, including a predominant cell population, myeloid-derived suppressor cells (MDSCs). Notably, the RT-induced MDSCs play a vital role in radioresistance. To enhance the efficacy of RT, numerous preclinical studies have elucidated the mechanisms by which RT modulates MDSCs, and evaluated the MDSC-targeted strategies to sensitize RT. Moreover, some clinical studies have explored drugs involved in MDSC-targeting to enhance the effectiveness of RT. However, though generally tolerable, the clinical benefits of combining these agents with RT are limited. Lacking specificity of MDSC-targeted agents is a major concern. Furthermore, several fundamental challenges complicate the investigation of MDSCs and their interplay with RT. These include the lack of specific biomarkers for MDSCs, their dynamic behavior during RT, differences between murine and human immune systems, the complexity of standard-of-care regimens, and the involvement of other immunosuppressive cell populations. Future investigations need to keep focusing on uncovering the features of MDSCs and their roles in RT, so that we can develop specific therapies to target MDSCs individually. This review covers the complicated regulatory network between RT and MDSCs, as well as current preclinical and clinical strategies targeting MDSC to sensitize RT, aiming to provide some insights and directions for cancer therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"855-880"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Cancer Therapy-Induced Cardiotoxicity in the Era of Spatial and Multi-Omics from Systemic Mechanisms to <i>In Situ</i> Microenvironments.","authors":"Cheng Gou, Qian Li, Ting Xiong, Shengzheng Lin, Kaining Wang, Jianhao Liu, Chuansong Xue","doi":"10.7150/jca.132588","DOIUrl":"https://doi.org/10.7150/jca.132588","url":null,"abstract":"<p><p>Cardio-oncology has emerged as a critical discipline addressing the cardiovascular sequelae of antineoplastic therapies. While traditional chemotherapy, targeted therapies, and immune checkpoint inhibitors (ICIs) have revolutionized cancer survival, they are frequently accompanied by cardiotoxicity ranging from asymptomatic left ventricular dysfunction to fulminant myocarditis. Current clinical strategies, relying heavily on echocardiography and serum biomarkers, often fail to detect early molecular perturbations or elucidate the complex multicellular interactions within the cardiac microenvironment. The advent of multi-omics technologies, genomics, transcriptomics, proteomics, and metabolomics, has provided systemic insights into these pathomechanisms. More recently, the integration of single-cell RNA sequencing (scRNA-seq) and spatial omics has enabled \"<i>in situ</i>\" visualization of cellular heterogeneity and intercellular communication, resolving the \"blind spots\" of bulk sequencing. This review synthesizes the current landscape of therapy-induced cardiotoxicity, highlights the limitations of conventional methodologies, and comprehensively examines how multi-dimensional omics strategies are reshaping our understanding of mechanisms, biomarker discovery, and precision cardioprotection.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"835-846"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Tumor Cells Detected Using EpAb3-5 as Prognostic Indicators in Head and Neck Squamous Cell Carcinoma.","authors":"Po-Chih Hsu, Chun-Fan Lung, Chan-Yen Kuo, Han-Chung Wu, Yi-Chiung Hsu","doi":"10.7150/jca.131794","DOIUrl":"https://doi.org/10.7150/jca.131794","url":null,"abstract":"<p><strong>Background: </strong>EpAb3-5, an anti-EpCAM (epithelial cell adhesion molecule) neutralizing antibody, enhances circulating tumor cell (CTC) detection, but its clinical and prognostic relevance in head and neck squamous cell carcinoma (HNSCC) remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed 66 HNSCC patients. CTCs were enumerated using EpAb3-5 and a commercial EpCAM-based platform (MACS), and tumor EpCAM expression detected using EpAb3-5 was assessed by immunohistochemistry. Associations with clinicopathologic features were evaluated, and survival outcomes were analyzed using Kaplan-Meier and Cox regression models, truncated at five years.</p><p><strong>Results: </strong>EpAb3-5 detected significantly more CTCs than MACS (p < 0.001), indicating greater detection sensitivity. Tumor EpCAM expression detected by EpAb3-5 correlated with nodal status (p < 0.01) but not T classification or overall stage. Although EpAb3-5-detected EpCAM expression alone was not an independent predictor of overall survival (OS) or disease-free survival (DFS), its integration with tumor staging revealed a context-dependent prognostic association. Specifically, low EpCAM expression assessed using EpAb3-5 identified early-stage patients with better OS (p < 0.05), whereas no significant survival differences were observed in advanced-stage disease.</p><p><strong>Conclusions: </strong>EpAb3-5 enhances CTC detection compared with a conventional EpCAM-based method and provides complementary prognostic information when interpreted alongside tumor staging. These findings indicate that EpCAM immunoreactivity assessed using EpAb3-5 may assist in refining risk stratification in early-stage HNSCC; however, these observations should be considered exploratory and warrant further validation in larger prospective cohorts.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"881-889"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Oxidative Balance Score and Colorectal Cancer: Insights from NHANES 1999-2018.","authors":"Danjing Chen, Bingqin Xie, Hua Fang, Huajing Chang, Wenxin Qiu, Jiangwang Fang, Yunli Wu, Xian-E Peng","doi":"10.7150/jca.126211","DOIUrl":"https://doi.org/10.7150/jca.126211","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have indicated an association between high antioxidant exposure and colorectal cancer (CRC) risk in elderly populations. However, the relationship between the oxidative balance score (OBS) and CRC risk in the general population remains unclear.</p><p><strong>Objective: </strong>In this study, we used the OBS, which is based on dietary and lifestyle factors, to assess the oxidative stress (OS) status of individuals and to explore the association between OBS and CRC risk in American adults.</p><p><strong>Methods: </strong>Overall, 44,482 participants from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were included in the cross-sectional study, of whom 340 had CRC. OBS, which consists of 20 dietary and lifestyle factors, was the exposure variable. Weighted multivariate logistic regression, subgroup analysis, and restricted cubic spline curves were used to assess the association between OBS and CRC. Sensitivity analyses were conducted to evaluate the robustness of the results.</p><p><strong>Results: </strong>Multiple logistic regression showed that the CRC risk decreased by 2.0% for each OBS unit added (<i>OR</i>= 0.98, 95%<i>CI</i>: 0.96-1.00, <i>P</i>=0.019). Compared with the lowest OBS reference group (T1), OBS in the highest tertile of OBS (T3) was associated with a reduced CRC risk (<i>OR</i>= 0.58, 95%<i>CI</i>: 0.39-0.84). Similarly, individuals in the highest dietary OBS tertile (T3) had a reduced CRC risk (<i>OR</i>= 0.63, 95%<i>CI</i>: 0.44-0.91), whereas no significant association was observed in lifestyle OBS and CRC.</p><p><strong>Conclusion: </strong>Higher OBS and dietary OBS were associated with CRC. A healthy lifestyle and antioxidant-rich diet may be useful for preventing CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"890-897"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orientin and Cancer Suppression: Molecular Mechanisms and Synergistic Effects.","authors":"Emad A Ahmed, Peramaiyan Rajendran","doi":"10.7150/jca.127661","DOIUrl":"https://doi.org/10.7150/jca.127661","url":null,"abstract":"<p><p>Orientin, a C-glycosyl flavonoid (luteolin-8-C-glucoside) naturally present in plants such as <i>Ocimum sanctum</i> (holy basil), <i>Trollius chinensis</i>, rooibos tea, and <i>Passiflora</i> species, exhibits a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects. In cancer research, orientin has been identified as a potent natural compound that can regulate several fundamental hallmarks of tumor progression, including excessive cell proliferation, resistance to apoptosis, angiogenic signaling, and metastatic dissemination. This review highlights orientin as a low-toxicity, naturally derived flavonoid that is generally well tolerated by healthy cells and may offer cytoprotective and antioxidant benefits, in contrast to conventional chemotherapeutics that often damage normal tissue, while selectively targeting cancer cells. The underlying molecular mechanisms responsible for orientin's inhibition of cancer progression, as well as its potential synergy with other therapies, are summarized. Collectively, these properties suggest a favorable pharmacological profile, supporting its consideration for clinical applications, especially in combination treatment approaches.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"847-854"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A squamous epithelial gene interaction perturbation network index for risk stratification in esophageal squamous cell carcinoma.","authors":"Chen Zhang, Huimin Wang, Huaping Wang, Xuexin Wang, Shan Tang, Feng Li, Li-Dong Wang, Jianqiu Sheng","doi":"10.7150/jca.132865","DOIUrl":"https://doi.org/10.7150/jca.132865","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) exhibits substantial molecular heterogeneity and unfavorable clinical outcomes. Current transcriptomic advances are shifting the focus from static gene expression profiles to the dynamic architecture of gene interaction networks. However, gene interaction perturbation signatures specific to ESCC remain poorly understood. This study aimed to develop a network-informed prognostic index derived from malignant epithelial cell signatures. In-house single-cell RNA sequencing data from 15 ESCC samples from the First Affiliated Hospital of Zhengzhou University were analyzed to identify dysregulated genes in malignant squamous epithelial cells. Then, a gene interaction perturbation network index (GIPNI) was constructed by systematically evaluating 75 combinations of machine-learning methods and validated across 3 independent cohorts. Associations between the GIPNI and genomic alterations, immune-related characteristics, and therapeutic response were also evaluated. Results showed ESCCs with high-GIPNI scores were associated with advanced clinicopathological features and overactivated mitotic cell cycle and epithelial cell differentiation pathways. Immune profiling suggested that low-GIPNI tumors had a more immune-infiltrated microenvironment. Notably, high-GIPNI ESCCs were associated with higher sensitivity to some common chemotherapeutic agents. Overall, the GIPNI provides a network-informed and malignant squamous cell-oriented framework for prognostic assessment in ESCC. This integrative approach may facilitate risk stratification and provide insights into individualized therapeutic strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"905-924"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Lipid Metabolism in the Progression of Breast Cancer.","authors":"Tong-Tong Liu, Meng-Meng Wang","doi":"10.7150/jca.128498","DOIUrl":"https://doi.org/10.7150/jca.128498","url":null,"abstract":"<p><p>Breast cancer is one of the most prevalent malignancies globally, it is closely associated with lipid metabolism reprogramming. Targeting lipid metabolism pathways has become a promising strategy for breast cancer treatment. Lipid metabolism encompasses the biochemical processes of lipid biosynthesis, catabolism, uptake, and post-synthetic modification. Dysregulation of these processes can promote tumorigenesis and cancer cell metastasis. This review summarizes four major facets of lipid metabolism, including fatty acid (FA) metabolism, cholesterol metabolism, phospholipid (PL) metabolism, and sphingolipid metabolism. It also discusses the roles of key molecules in these pathways in breast cancer, including FA synthase (FASN), cluster of differentiation 36 (CD36), and acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecules may improve therapeutic responses, overcome drug resistance, and reshape the tumor immune microenvironment by regulating FA synthesis and lipid uptake. Targeting lipid metabolic pathways may provide potential biomarkers for patient stratification and therapeutic guidance, and may also offer new opportunities for cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"898-904"},"PeriodicalIF":3.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Targeting of Oxidative Phosphorylation in Microsatellite Instability-High Gastric Cancer.","authors":"Bing Ang, Yi Bai, Xiyue Deng, Qiong Wu, Yuqian Wang, Shanshan Xu, Weixin Zhang, Yang Li, Dapeng Chen, Ruixi Li, Siyang Li, Zhigang Zhao, Yamin Zhang","doi":"10.7150/jca.127225","DOIUrl":"https://doi.org/10.7150/jca.127225","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the third leading cause of cancer-related mortality worldwide. According to The Cancer Genome Atlas (TCGA), it can be classified into four molecular subtypes, including microsatellite instability (MSI) and genomically stable (GS) subtypes, which display distinct clinical and pathological features. However, differences in their tumor microenvironment, particularly metabolic reprogramming, remain poorly understood.</p><p><strong>Methods: </strong>Single-cell RNA sequencing data from gastric cancer patients classified as GS or MSI were enrolled. Cell clusters were identified and annotated to compare cellular landscapes between subtypes. Differential gene expression and pathway analyses were performed among malignant epithelial cells. Key genes related to oxidative phosphorylation were identified using LASSO regression, and their expression was further validated in the TCGA dataset. Patient-derived xenograft models were used to compare tumor growth rates, ATP levels, and expression of oxidative phosphorylation -related genes.</p><p><strong>Results: </strong>Single-cell transcriptomic analysis revealed eight major cell types in MSI tumors. Compared to the GS subtype, MSI samples showed significantly greater infiltration of T cells and a lower proportion of epithelial cells. Malignant cells from MSI samples exhibited increased activity of oxidative phosphorylation pathways. LASSO regression identified five oxidative phosphorylation-related genes that were consistently overexpressed in MSI tumors in both single-cell and TCGA datasets. In Patient-derived xenograft models, MSI tumors grew more rapidly and demonstrated higher ATP levels and elevated expression of the five oxidative phosphorylation-related genes compared to MSS tumors.</p><p><strong>Conclusion: </strong>Our study reveals enhanced oxidative phosphorylation metabolism in MSI gastric cancer at single-cell resolution and identifies five oxidative phosphorylation-related genes that may serve as potential therapeutic targets for this subtype.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"797-807"},"PeriodicalIF":3.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal CT-based deep learning radiomics for predicting prognosis in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a two-center study.","authors":"Xinyang Hu, Wubulaishan Maitudi, Xi Chen, Lina Zhao, Qingsong Pang","doi":"10.7150/jca.126804","DOIUrl":"https://doi.org/10.7150/jca.126804","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and validate a longitudinal deep-learning based survival prediction model for esophageal squamous cell carcinoma (ESCC) patients who received definitive concurrent chemoradiotherapy (CCRT).</p><p><strong>Methods: </strong>A total of 257 ESCC patients from two centers were recruited. Among them, 205 patients were in the training cohort and 52 in the external testing cohort. The CrossFormer algorithm was utilized to extract features from pre- and post- treatment CECT scans. We constructed clinical, Delta-radiomics and deep-learning models. Models were evaluated by the C-index and integrated Brier score (iBS). Prognostic stratification was performed based on risk scores, and model interpretability was evaluated using Grad-CAM and SurvSHAP(t).</p><p><strong>Results: </strong>The Fusion model demonstrated superior predictive performance, achieving a C-index of 0.768 (95% CI: 0.731-0.804) in the training cohort and 0.734 (95% CI:0.665-0.803) in the testing cohort. The Fusion model also showed the best calibration (Training cohort: iBS=0.096; Testing cohort: iBS=0.151). Patients were stratified into high-risk and low-risk groups based on risk scores, with significant differences in overall survival (OS) between the groups (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>We developed a model integrating longitudinal CECT scans to predict OS in ESCC patients undergoing CCRT. The results highlight the importance of capturing tumor changes during treatment for accurate prognostic stratification. The model shows its potential for guiding personalized treatment strategies in clinical practice.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"808-818"},"PeriodicalIF":3.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting MUC16 to Reverse Anoikis Resistance: A Promising Strategy for Metastatic Lung Adenocarcinoma Therapy.","authors":"Kulsoom, Wajahat Ali, Zhe Ma, Wen Cai, Zhenlong Wang, Fu Wang","doi":"10.7150/jca.131494","DOIUrl":"https://doi.org/10.7150/jca.131494","url":null,"abstract":"<p><strong>Background: </strong>Although the mucin glycoprotein <i>MUC16</i> is well established as an oncogenic biomarker in ovarian cancer, its mechanistic contribution to lung adenocarcinoma (LUAD) remains poorly defined. This study integrates multi-omics profiling and functional validation to uncover <i>MUC16</i> as a novel determinant of detachment-induced survival in LUAD.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from TCGA-LUAD and GEO cohorts were analyzed to identify differentially expressed anoikis-related genes. Functional enrichment, GSVA, and network analyses delineated key signaling pathways. Multi-omic integration including copy-number, methylation, immune infiltration, and pharmacogenomic data was used to explore upstream regulatory mechanisms. Experimental assays were performed in A549 cells following siRNA-mediated <i>MUC16</i> silencing, assessed by qRT-PCR, wound-healing, and transwell migration analyses.</p><p><strong>Results: </strong>Nineteen overlapping anoikis-related differentially expressed genes (ARDEGs) were identified, with <i>MUC16</i> displaying the most significant upregulation in LUAD and a strong association with poor overall survival (HR = 1.04, p < 0.001). Pathway enrichment indicated activation of cell-adhesion, Hippo, and PI3K-AKT signaling networks. Multi-omic analysis revealed that promoter hypomethylation and copy-number gain drive <i>MUC16</i> overexpression, which correlates with reduced cytotoxic T-cell infiltration and an immunosuppressive microenvironment. Functionally, <i>MUC16</i> knockdown diminished cell adhesion, migration, and wound closure, consistent with loss of detachment survival capacity.</p><p><strong>Conclusion: </strong>This work establishes <i>MUC16</i> as a mechanistic mediator of metastatic competence in LUAD, acting through adhesion-linked PI3K-AKT signaling to protect tumor cells from detachment-induced apoptosis. Therapeutic inhibition of MUC16 may restore apoptotic susceptibility and suppress metastatic spread in lung cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"819-834"},"PeriodicalIF":3.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}