Translational cancer research最新文献

{"title":"AMOT mediates YAP1 activation and promotes the cell progression and glycolysis in non-small cell lung cancer by modulating the Hippo signaling pathway.","authors":"Yihao Guo, Wendong Wang, Jinsong Li, Jun Zhang","doi":"10.21037/tcr-2026-1555","DOIUrl":"https://doi.org/10.21037/tcr-2026-1555","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) exhibits aggressive cell progression and profound metabolic reprogramming. This study investigated the clinical significance, functional role, and molecular mechanism of the Angiomotin (AMOT)/Yes-associated protein 1 (YAP1)/Hippo axis in regulating NSCLC growth and glycolysis.</p><p><strong>Methods: </strong>AMOT expression was analyzed in 68 paired NSCLC and adjacent normal tissues. <i>In vitro</i> gain- and loss-of-function assays (proliferation, apoptosis, and Transwell migration) and normalized intracellular metabolic measurements (ATP, lactate, and glucose) were performed in A549 and NCI-H1299 cell lines. The underlying Hippo signaling mechanism was evaluated via Co-IP, Western blotting, The Cancer Genome Atlas (TCGA) correlation analysis, and subcutaneous xenograft mouse models.</p><p><strong>Results: </strong>AMOT was significantly upregulated in NSCLC tissues, correlating with larger tumor size (≥4 cm), advanced clinical stage, and poorer overall survival. <i>AMOT</i> silencing markedly suppressed cell proliferation and migration while inducing apoptosis. AMOT and YAP1 exhibited a strong positive co-expression pattern. <i>YAP1</i> knockdown significantly inhibited proliferation, migration, intracellular glycolysis, and <i>in vivo</i> tumor growth, effects that were partially rescued by AMOT overexpression. Mechanistically, AMOT inhibited LATS1 and YAP1 phosphorylation, promoting YAP1 stabilization and nuclear transactivation, thereby driving tumor progression and glycolytic reprogramming.</p><p><strong>Conclusions: </strong>The AMOT/YAP1/Hippo axis acts as a crucial driver of NSCLC progression and aerobic glycolysis, offering a promising therapeutic target for NSCLC intervention.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"681"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184395","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":"FBXO17 regulates the malignant progression of colorectal cancer via the Wnt/β-catenin pathway.","authors":"Enyan Tang, Yijie Xiao, Xiaohong Qian, Shufei Li, Bin Chen","doi":"10.21037/tcr-2026-0704","DOIUrl":"https://doi.org/10.21037/tcr-2026-0704","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, often presenting without apparent early symptoms, and most patients are diagnosed at an advanced stage with a poor prognosis. F-box protein 17 (FBXO17) is up-regulated in various tumors and may represent a potential prognostic marker in CRC. This study sought to elucidate FBXO17's specific role in CRC and the underlying mechanism.</p><p><strong>Methods: </strong>Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), together with Western blot, was applied to determine FBXO17 expression in CRC cell lines. FBXO17-silenced and FBXO17-overexpressing CRC cells were established using a lentiviral system and liposome transfection technology, respectively. Cell counting kit-8, Transwell, and wound healing assays, as well as Western blot, were used to assess CRC cell proliferation, invasion, and migration, and to examine Wnt/β-catenin pathway activation. Intracellular reactive oxygen species (ROS), Fe²⁺, malondialdehyde (MDA), oxidized glutathione, and reduced glutathione, along with GPX4 and PTGS2 protein expression, were determined to assess CRC cell ferroptosis.</p><p><strong>Results: </strong>Compared with human normal colon cells, human CRC cells exhibited generally high FBXO17 expression. Silencing FBXO17 led to decreased CRC cell proliferation, invasion, and migration, attenuated Wnt/β-catenin pathway activation, and enhanced ferroptosis, whereas overexpression of FBXO17 reversed these effects by enhancing CRC cell proliferation, invasion, and migration, activating the Wnt/β-catenin pathway, and suppressing ferroptosis. Furthermore, treatment with ferrostatin-1 (ferroptosis inhibitor) or CHIR-99021 (Wnt/β-catenin pathway agonist) enhanced the proliferation, invasion, and migration of FBXO17-silenced CRC cells while attenuating ferroptosis.</p><p><strong>Conclusions: </strong>Silencing FBXO17 can promote CRC cell ferroptosis but inhibit proliferation, invasion, and migration through suppression of Wnt/β-catenin pathway activation.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"686"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184452","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":"Expression, prognostic association, and immune microenvironment correlates of <i>C4orf50</i> in breast cancer: a The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) bioinformatics study.","authors":"Sihang Lin, Lixia Liu, Jiayu Guan, Jie Wang, Chuanrong Cen, La Wei, Huawei Yang","doi":"10.21037/tcr-2026-1590","DOIUrl":"https://doi.org/10.21037/tcr-2026-1590","url":null,"abstract":"<p><strong>Background: </strong>Chromosome 4 open reading frame 50 (<i>C4orf50</i>) is a poorly characterized gene whose expression pattern and clinical relevance in breast cancer remain unclear. We aimed to evaluate the expression, prognostic association, immune microenvironment correlates, and transcriptional features associated with <i>C4orf50</i> in breast cancer.</p><p><strong>Methods: </strong>RNA-sequencing and clinical data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) cohort were analyzed. <i>C4orf50</i> expression was compared between tumor and normal tissues and across clinicopathological subgroups. Continuous <i>C4orf50</i> expression was evaluated in Cox proportional hazards models, including stage- and molecular-subtype-stratified sensitivity models. Immune-cell transcriptional enrichment was quantified using single-sample gene set enrichment analysis (ssGSEA) with the LM22 leukocyte signature matrix representing 22 immune-cell populations. Raw and Consensus Purity Estimate (CPE)-adjusted associations were examined, together with tumor microenvironment scores generated using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. Immune-checkpoint expression, patient-level coexpression, Gene Ontology, MSigDB C2 gene set enrichment analysis (GSEA), and consensus cancer-hallmark enrichment were also assessed.</p><p><strong>Results: </strong><i>C4orf50</i> expression was higher in 1,093 breast tumor samples than in 111 normal samples (Wilcoxon P=4.6×10⁻¹¹; Cliff's delta =0.379), whereas no robust associations with pathological stage, molecular subtype, or receptor status remained after multiple-testing correction. In the primary stage-by-subtype-stratified Cox model, higher continuous <i>C4orf50</i> expression was associated with poorer overall survival [hazard ratio (HR) per 1 standard deviation =1.41, 95% confidence interval (CI): 1.19-1.67; P<0.001]. The median-based Kaplan-Meier analysis was not significant (P=0.38). <i>C4orf50</i> expression correlated positively with the ESTIMATE Immune Score (rho =0.372), Stromal Score (rho =0.198), and ESTIMATE Score (rho =0.340; all false discovery rate values <0.001). Tumor-purity adjustment attenuated but did not eliminate most associations with LM22 immune-cell and immune-checkpoint signatures. Coexpressed transcripts were enriched in regulated exocytosis, calcium-dependent exocytosis, dense-core granule exocytosis, and vesicle-related processes. No integrated cancer hallmark reached significance after multiple-testing correction.</p><p><strong>Conclusions: </strong><i>C4orf50</i> is overexpressed in breast cancer and its continuous expression is associated with overall survival and immune-related transcriptional features in TCGA-BRCA. These observational findings do not establish a causal role for <i>C4orf50</i> and require validation in independent cohorts and experimental models.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"684"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184459","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":"Integrating multimodal data for precise subtyping and prognostication in patients with pulmonary mucinous adenocarcinoma.","authors":"Weiwei Yang, Chen Chen, Lue Li, Zehao Chen, Ziyi Chen, Hanbo Le, Yongkui Zhang, Wangyu Zhu","doi":"10.21037/tcr-2026-1241","DOIUrl":"https://doi.org/10.21037/tcr-2026-1241","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary mucinous adenocarcinoma (PMA) represents a rare lung adenocarcinoma subtype, characterized by a lack of comprehensive pathological classification and prognostic factors. In this study, we propose a multimodal machine learning (ML) framework that integrates multiple data modalities to enhance PMA subtype classification and prognostic prediction.</p><p><strong>Methods: </strong>This retrospective study enrolled 175 primary PMA cases with details of demographic, histopathological, computed tomography (CT) imaging, and epithelial growth factor receptor (<i>EGFR</i>) mutation data. Least absolute shrinkage and selection operator (LASSO) regularized logistic regression model was utilized for histological classification, and Cox proportional hazards model was employed for survival prediction with internal validation.</p><p><strong>Results: </strong>Pure mucinous adenocarcinoma presented a higher prevalence of smaller radiographic or pathological tumor size, lower lobe localization, lower rates of lymph node metastasis and spread through air spaces (STAS), early pathological stage, carcinoembryonic antigen (CEA) ≤5 ng/mL, spiculated margin, Ki-67 low expression and lower frequency of <i>EGFR</i> exon 19 deletion (P=0.002, 0.003, <0.001, <0.001, 0.001, <0.001, 0.002, 0.03, 0.02, 0.001, respectively) compared to mix mucinous and mucin-secreting adenocarcinoma. The ML-derived nomogram achieved discriminative ability, with an area under the curve (AUC) of 0.792 in the training set and 0.687 in the validation set, and exhibited satisfactory calibration for the preoperative diagnosis of pure mucinous adenocarcinoma. Multivariate Cox modeling identified higher CEA levels, and <i>EGFR</i> exon 19 deletion as independent prognostic factors in PMA (P=0.04, 0.049, respectively). Moreover, Kaplan-Meier curves revealed significantly different outcomes between low- and high-risk groups stratified by the nomogram score (P<0.001).</p><p><strong>Conclusions: </strong>Pulmonary pure mucinous adenocarcinoma exhibited lower malignancy compared to the mixed mucinous and mucin-secreting type. The nomogram model developed and validated in this study exhibited promising efficacy in predicting histological subtype preoperatively and survival in patients with PMA, offering guidance for clinicians in diagnosis and prognosis prediction.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"708"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184484","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":"Lnc-TIM3 promotes acute lymphoblastic leukemia progression through miR-5094-mediated regulation of TIM3.","authors":"Jing Sun, Jiou Zhao, Wenfeng Fu, Huimin Li, Meiyun Kang, Yongjun Fang, Yaping Wang","doi":"10.21037/tcr-2026-1285","DOIUrl":"https://doi.org/10.21037/tcr-2026-1285","url":null,"abstract":"<p><strong>Background: </strong>Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children and is associated with dysregulated long non-coding RNAs (lncRNAs), some of which may serve as potential biomarkers and therapeutic targets. However, the expression pattern and biological role of Lnc-TIM3 in pediatric ALL remain poorly understood. This study aimed to characterize Lnc-TIM3 expression in pediatric ALL and investigate its functional role and underlying regulatory mechanism, with a particular focus on the Lnc-TIM3/miR-5094/TIM3 axis.</p><p><strong>Methods: </strong>The expression levels of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, DNA synthesis, migration, and invasion capabilities were assessed using Cell Counting Kit-8 (CCK-8) assays, soft-agar colony assays, flow cytometry, and <i>in vitro</i> transduction experiments, respectively. <i>In vivo</i> validation was conducted using a zebrafish model. The competitive endogenous RNA (ceRNA) regulatory mechanism was examined using dual-luciferase reporter assays, whereas protein expression was assessed by Western blotting.</p><p><strong>Results: </strong><i>Lnc-TIM3</i> was highly expressed in primary bone marrow samples from patients with ALL and in ALL cell lines. <i>Lnc-TIM3</i> knockdown reduced <i>TIM3</i> expression and significantly inhibited ALL progression in both <i>in vitro</i> and <i>in vivo</i> models. Furthermore, inhibition of miR-5094 partially reversed the phenotypic effects of Lnc-TIM3 knockdown. Changes in GAL9 and downstream signaling components suggested, but did not establish, the involvement of TIM3/GAL9-related signaling.</p><p><strong>Conclusions: </strong><i>Lnc-TIM3</i> promotes the progression of ALL by binding to <i>miR-5094</i> and upregulating <i>TIM3</i> expression.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"682"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184479","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":"Extracellular adenosine triphosphate upregulates S100A4 expression and promotes the migration and invasion of breast cancer cells via P2Y2/SOX9 signaling.","authors":"Yue Cui, Fengming Ran, Guangxiong Ruan, Sheng Huang, Ying Liu","doi":"10.21037/tcr-2026-2245","DOIUrl":"https://doi.org/10.21037/tcr-2026-2245","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME), composed of tumor cells, mesenchymal cells, and diverse extracellular molecules, plays a pivotal regulatory role in tumor initiation, malignant progression, and the development of anti-cancer therapeutic resistance. Extracellular adenosine triphosphate (ATP) is a critical bioactive signaling molecule in the TME. Previous studies from our group have confirmed that extracellular ATP is extensively involved in multiple malignant phenotypes of prostate cancer and breast cancer, including tumor cell migration, invasion, chemotherapeutic resistance, and the maintenance of cancer stem cell properties. In our prior work, we demonstrated that extracellular ATP acts on stromal fibroblasts in the breast cancer microenvironment to facilitate the formation of a pro-tumorigenic niche. However, the full molecular mechanism governing this regulatory axis remains incompletely elucidated. Here, we aim to uncover its underlying mechanism, thereby providing new insights for the development of breast cancer therapeutic strategies.</p><p><strong>Methods: </strong>In this study, primary breast cancer cells isolated from clinical breast cancer tissue specimens were used as the core research model. A series of experimental approaches were applied, including extracellular ATP stimulation assays, P2 receptor intervention, <i>SOX9</i> gene loss-of-function manipulations, S100A4 expression detection at both transcriptional and translational levels, transwell invasion assays of primary breast cancer cells and fibroblasts, to evaluate the formation efficiency of cancer-associated fibroblasts (CAFs).</p><p><strong>Results: </strong>Our experimental results revealed that extracellular ATP can significantly upregulate the expression of S100A4 in primary breast cancer cells. In terms of mechanism, this regulatory effect is mediated by the P2 receptor-SOX9 signaling axis. Specifically, the binding of extracellular ATP to its membrane P2 receptors activates the downstream transcription factor SOX9, which further transcriptionally promotes the expression of target gene <i>S100A4</i>. Functional validation experiments confirmed that this signaling cascade subsequently enhances the migration and invasion capacities of breast cancer cells.</p><p><strong>Conclusions: </strong>This study identified a novel regulatory pathway mediated by extracellular ATP in the breast cancer microenvironment; that is, the P2 receptor-SOX9-S100A4 signaling axis, which promotes the malignant progression of breast cancer and the remodeling of the tumor stroma. These findings not only expand the mechanistic understanding of extracellular ATP in the tumor-promoting microenvironment but also provide a potential new molecular for the targeted intervention of breast cancer metastatic progression and stromal therapy resistance.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"714"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184494","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":"URGCP promotes osteosarcoma progression by regulating the ESCRT-III subunit CHMP4B.","authors":"Yue Wang, Yuhuai Wu, Bin Zhou, Jianping Liu","doi":"10.21037/tcr-2026-1420","DOIUrl":"https://doi.org/10.21037/tcr-2026-1420","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents, with a persistently poor prognosis due to limited effective therapeutic targets. Identifying key oncogenic drivers and their regulatory networks is critical for developing novel targeted therapies to improve clinical outcomes. In this study, we aimed to investigate the expression pattern, diagnostic value, and functional role of upregulator of cell proliferation (URGCP) in OS, as well as to elucidate its downstream molecular mechanism, specifically focusing on the URGCP-CHMP4B regulatory axis.</p><p><strong>Methods: </strong>We conducted a bioinformatics analysis of public datasets (Gene Expression Omnibus) to identify the dysregulation and diagnostic value of <i>URGCP</i> in OS. <i>In vitro</i> functional assays were conducted in <i>URGCP</i> knockdown MG-63 OS cells, including Cell Counting Kit-8 (CCK-8) proliferation assay, flow cytometry-based apoptosis detection, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), and western blotting. A xenograft mouse model was established to validate the <i>in vitro</i> findings. Rescue experiments were conducted by overexpressing CHMP4B in <i>URGCP</i> knockdown cells to decipher the downstream effector of URGCP.</p><p><strong>Results: </strong>Bioinformatics analyses revealed that <i>URGCP</i> was significantly upregulated in OS tissues and exhibited diagnostic value. Silencing <i>URGCP</i> significantly inhibited OS cell proliferation and induced apoptosis <i>in vitro</i>, and suppressed tumor growth <i>in vivo</i>. Mechanistically, <i>in vitro</i> and <i>in vivo</i> <i>URGCP</i> knockdown led to the downregulation of CHMP4B, a core subunit of the endosomal sorting complex required for transport III (ESCRT-III), which is critical for regulating cell proliferation and apoptosis. Crucially, restoring CHMP4B expression <i>in vitro</i> effectively reversed the anti-proliferative and pro-apoptotic effects induced by <i>URGCP</i> silencing.</p><p><strong>Conclusions: </strong>Our study identifies URGCP as an oncoprotein in OS that exerts its tumor-promoting effects, at least in part, by positively regulating CHMP4B. The URGCP-CHMP4B axis represents a potential therapeutic target for OS treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"692"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184566","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":"Multi-omics integration identifies PON2 as a prognostic biomarker and mediator of tumor microenvironment remodeling in gallbladder cancer.","authors":"Jian Yang, Lingbo Hu, Chao Yang, Haoyang Bei, Yulian Wu","doi":"10.21037/tcr-2026-1620","DOIUrl":"https://doi.org/10.21037/tcr-2026-1620","url":null,"abstract":"<p><strong>Background: </strong>Gallbladder cancer (GBC) is an aggressive biliary tract malignancy with limited therapeutic options and poor prognosis. Tumor microenvironment (TME) remodeling contributes substantially to GBC progression; however, the molecular drivers linking malignant epithelial programs to microenvironmental alterations remain poorly defined. This study aimed to characterize the cellular ecosystem of GBC and identify clinically relevant molecular targets associated with tumor progression and TME remodeling.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (RNA-seq) data from 10 GBC tissues and 4 matched adjacent normal tissues were analyzed to define the cellular landscape of GBC. Unsupervised clustering, cell-type annotation, and copy number variation analysis were used to characterize TME composition and identify malignant epithelial populations. Integrated analyses of single-cell transcriptomic, bulk RNA-seq, and tumor proteomic datasets were performed to screen candidate prognostic biomarkers. The clinical relevance of the candidate gene was evaluated by survival analysis and validated in clinical GBC specimens using immunohistochemistry and quantitative real-time polymerase chain reaction. Functional assays were conducted in GBC cell lines to assess its effects on tumor cell proliferation and migration. Cell-cell communication analysis was further used to explore potential interactions between malignant epithelial cells and non-malignant microenvironmental components.</p><p><strong>Results: </strong>Single-cell profiling revealed substantial cellular heterogeneity within the GBC microenvironment and identified malignant epithelial clones with distinct transcriptional programs. Multi-omics integration identified paraoxonase 2 (PON2) as a potential prognostic biomarker in GBC. Elevated PON2 expression was validated in clinical GBC specimens and was associated with worse overall survival. <i>In vitro</i> knockdown of PON2 significantly suppressed the proliferation and migration of GBC cells. Further single-cell analysis showed that the PON2-high malignant epithelial state was accompanied by remodeling of endothelial and stromal subpopulations. Cell-cell communication analysis suggested that PON2-high malignant epithelial cells exhibited enhanced interactions with endothelial cells, fibroblasts, and pericytes through specific ligand-receptor networks, indicating a potential role of PON2 in shaping a pro-tumorigenic microenvironment.</p><p><strong>Conclusions: </strong>This multi-omics study identifies PON2 as a clinically relevant biomarker associated with GBC progression and TME remodeling. PON2 may serve as a prognostic indicator and potential therapeutic target, providing new insights into TME-directed translational strategies for GBC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"678"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184342","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":"Selenium metabolism-related gene <i>TXNRD1</i> drives tumor progression and microenvironment remodeling in oral squamous cell carcinoma.","authors":"Jun Zhan, Qixiang Sun, Wenyuan Zhu, Xiao Lu, Yao He","doi":"10.21037/tcr-2026-1753","DOIUrl":"https://doi.org/10.21037/tcr-2026-1753","url":null,"abstract":"<p><strong>Background: </strong>Selenium metabolism is implicated in redox regulation and tumor progression, yet its role in oral squamous cell carcinoma (OSCC) remains elusive. Thioredoxin reductase 1 (TXNRD1), a core selenoprotein, has been linked to malignant phenotypes, but its clinical relevance and biological functions in OSCC require further elucidation. Therefore, this study aimed to systematically investigate the prognostic value and biological functions of TXNRD1 in OSCC through multi-omics analysis and experimental validation.</p><p><strong>Methods: </strong>We integrated multi-omics data from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB) to systematically screen selenium metabolism-related prognostic genes. Least absolute shrinkage and selection operator (LASSO) regression, single-cell transcriptomics GSE103322, and immune infiltration analyses were applied to evaluate the clinical value and microenvironmental features of TXNRD1. Furthermore, we established stable TXNRD1-knockdown OSCC cell lines HSC-2 using lentiviral-mediated short hairpin RNA (shRNA), and performed Cell Counting Kit-8 (CCK-8) proliferation assays, colony formation assays, and flow cytometry to validate its functional roles <i>in vitro</i>.</p><p><strong>Results: </strong>TXNRD1 was identified as a key selenium-related risk gene. It was significantly overexpressed in OSCC tissues and strongly correlated with poor overall survival area under the curve [area under the curve (AUC) =0.750]. Functional enrichment and single-cell analyses revealed that TXNRD1-high cancer cells were enriched in cell-cycle pathways (E2F targets, G2M checkpoint) and exhibited enhanced intercellular communication via MIF, LAMININ, and SPP1 pathways, along with associations with immune checkpoint genes PDCD1 and LAG3. Critically, our <i>in vitro</i> experiments demonstrated that TXNRD1 knockdown significantly suppressed OSCC cell viability and colony formation. Flow cytometric analysis further showed that TXNRD1 depletion induced a marked S-phase cell cycle arrest and significantly promoted apoptosis. Moreover, molecular docking predicted GSK591 as a potential compound targeting TXNRD1.</p><p><strong>Conclusions: </strong>TXNRD1 drives OSCC progression through a dual mechanism-facilitating S-phase progression and suppressing apoptosis-and represents a promising prognostic biomarker and therapeutic target in OSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"698"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184454","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":"Cellular immunotherapy for lung cancer: current clinical evidence, translational challenges, and future perspectives: a narrative review.","authors":"Nannan Ma, Chunxiang Shang","doi":"10.21037/tcr-2026-1627","DOIUrl":"https://doi.org/10.21037/tcr-2026-1627","url":null,"abstract":"<p><strong>Background and objective: </strong>Lung cancer remains a leading cause of cancer-related mortality. Cellular immunotherapy has achieved major advances in hematologic malignancies, but translation to lung cancer is constrained by antigen heterogeneity, limited trafficking and persistence, an immunosuppressive tumor microenvironment (TME), manufacturing complexity, and on-target off-tumor toxicity. This narrative review summarizes current clinical evidence, major translational barriers, and future development strategies for cellular immunotherapy in lung cancer.</p><p><strong>Methods: </strong>PubMed, Web of Science, Embase, and ClinicalTrials.gov were searched from database inception to 1 June 2026 using Medical Subject Headings (MeSH) and free-text terms. Evidence on chimeric antigen receptor T-cell (CAR-T), T-cell receptor-engineered T-cell (TCR-T), tumor-infiltrating lymphocyte (TIL), natural killer (NK), chimeric antigen receptor natural killer (CAR-NK), and cancer vaccine-based strategies was reviewed, with priority given to non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).</p><p><strong>Key content and findings: </strong>Most lung-cancer cellular therapy studies remain early phase. TIL therapy has demonstrated clinical activity in NSCLC, while EGFR, MSLN, CEA, MUC1, PD-L1, B7-H3, and DLL3 are representative targets under investigation for CAR-based approaches; NY-ESO-1 and KK-LC-1 are representative TCR-T targets. Major barriers include antigen escape, poor tumor infiltration, HLA restriction or loss, immunosuppressive signaling, cellular exhaustion, limited persistence, manufacturing burden, and treatment-related toxicity. Current optimization strategies include gene editing, chemokine-receptor engineering, armored or logic-gated receptors, safety switches, optimized lymphodepletion, and rational combinations with other anticancer therapies.</p><p><strong>Conclusions: </strong>Cellular immunotherapy is a promising but still developing strategy for lung cancer. Future studies should prioritize biomarker-guided patient selection, safer and more persistent cell products, scalable manufacturing, and prospective clinical validation of rational combination strategies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 9","pages":"717"},"PeriodicalIF":2.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184425","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}