Carcinogenesis最新文献

{"title":"Plasma proteomic profiling identified prognostic indicators with therapeutic potential for colorectal cancer.","authors":"Xuan Xie, Jiahao Zhou, Qingbin Wu, Jing Sun, Chi Shu, Jun Huang, Changtao Li, Xin Wang, Xia Shen, Xue Li, Zhipeng Luo, Chuan Xu, Ziqiang Wang, Yazhou He","doi":"10.1093/carcin/bgag001","DOIUrl":"10.1093/carcin/bgag001","url":null,"abstract":"<p><p>Plasma proteins have been reported as predictors and potential targets for reducing colorectal cancer (CRC) risk. However, their potential roles in CRC prognosis remain unexplored. We measured plasma levels of 367 neuro-related proteins in CRC patients from the West China Hospital (WCH) cohort (N = 150, median follow-up = 46.72 months) via proximity extension assay. The least absolute shrinkage and selection operator penalized Cox regression identified five overall survival (OS)-and eleven disease-free survival-associated proteins, and the multiprotein signature for OS prediction was then validated in the UK Biobank (UKB) cohort (N = 1133). To overcome possible effects from confounders, we then employed Mendelian randomization analysis leveraging protein quantitative trait loci to investigate associations between genetically determined protein concentration and OS and cancer-specific survival of CRC in the UKB. We found that multiprotein signature developed in the WCH cohort (c-index = 0.784, 95% CI = 0.713-0.855) showed significant discriminative ability in the external UKB cohort (c-index = 0.616, 95% CI = 0.559-0.673). A significant association between genetically determined PD-L1 and OS (P = 0.043, HR = 1.53, 95% CI = 1.01-2.29) was observed, although we did not find strong evidence for colocalization. Additionally, single-cell and spatial transcriptome analyses illustrated PD-L1 expression localized predominantly to epithelial cells and immune cells (especially myeloid cells) in CRC tissue. The potential interactions of identified proteins were evaluated in the STRING database. Druggability evaluation also supported PD-L1 as a potential therapeutic target for CRC. Taken together, this study established multiprotein signatures for CRC prognosis and identified plasma PD-L1 as a possible biomarker and therapeutic target.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CarD-T: an automated pipeline for the nomination and analysis of potential human carcinogens.","authors":"Jamey O'Neill, Gudur Ashrith Reddy, Nermeeta Dhillon, Osika Tripathi, Ludmil Alexandrov, Parag Katira","doi":"10.1093/carcin/bgaf074","DOIUrl":"10.1093/carcin/bgaf074","url":null,"abstract":"<p><p>The identification and classification of carcinogens is critical in cancer epidemiology, necessitating updated methodologies to manage the burgeoning biomedical literature. We introduce the Carcinogen Detection via Transformers (CarD-T) framework, combining transformer-based machine learning with probabilistic analysis to efficiently nominate potential carcinogens from scientific texts. Trained on 60% of established carcinogens, CarD-T correctly identifies all remaining known carcinogens and nominates ∼1600 potential new carcinogens. Comparative assessment against GPT-4 reveals CarD-T's comparable precision (0.896 versus 0.903), and superior recall (0.853 versus 0.757), implying an improved ability to nominate potential carcinogens for further evaluation. CarD-T associates each nominated entity with relevant scientific literature, allowing for additional analysis of conflicting implications over time through a Bayesian probabilistic carcinogen denomination analysis. The framework also provides rich insights into carcinogenesis associated research, revealing significant shifts in research focus on carcinogenic agents over time, from chemical carcinogens to broader categories including biological agents, environmental factors and lifestyle choices. We establish the CarD-T framework as a locally deployable, computationally inexpensive, and robust tool for identifying and nominating potential carcinogens from vast biomedical literature. This framework enhances the agility of public health responses to carcinogen identification, setting a new benchmark for automated, scalable toxicological investigations.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370136","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":"Δ133p53 isoform enhances TLR4 function to promote tumor growth.","authors":"Sasini Polwatta Lekamlage, Alexandra N Boix De Jesus, Adriana Machado Saraiva, Catherine Drummond, Harrison Dolan, Francesc March de Ribot, Janice A Royds, Sunali Mehta, Antony W Braithwaite, Noelyn A Hung, Tania L Slatter","doi":"10.1093/carcin/bgaf051","DOIUrl":"10.1093/carcin/bgaf051","url":null,"abstract":"<p><p>Tumor protein 53 (TP53) acts as a tumor suppressor and is often mutated in cancer. Isoforms of TP53, such as the Δ133p53 family, can promote tumor growth and metastasis. Therefore, targeting Δ133p53 function may represent a new strategy for preventing tumor metastasis. To inform the identification of proteins to target in Δ133p53-expressing tumors, changes at the cell surface were characterized. Inhibition of cell surface trafficking in a mouse model syngrafted with tumors expressing proteins similar to Δ133p53 (Δ122p53) was associated with reduced tumor growth and metastasis. After confirming that changes at the cell surface were important for Δ133p53 tumor promotion, characterization of protein changes at the Δ133p53/Δ122p53 cell surface revealed increased expression of the toll-like receptor 4 (TLR4) and the TLR4 agonist, apoptosis inhibitor 5. Furthermore, inhibition of TLR4 was sufficient to reduce Δ122p53 tumor growth. Altogether, these results suggest a role for Δ133p53 in contributing to tumor progression by stimulating TLR4 function. Furthermore, targeting changes at the cell surface can reduce Δ133p53 tumor promotion.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943957","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":"Development of a nomogram for the prediction of postoperative survival in hepatoid adenocarcinoma of the stomach.","authors":"Kang Wang, Yusong Chen, Xiaoli Li, Xinshuo Li, Yuqian Zhai, Yudan Yang, Haochen Li, Yan Wang, Ming Gao","doi":"10.1093/carcin/bgaf081","DOIUrl":"10.1093/carcin/bgaf081","url":null,"abstract":"<p><p>This study developed a prognostic nomogram for hepatoid adenocarcinoma of the stomach (HAS) using clinicopathological data from 61 surgically treated patients (First Affiliated Hospital of Zhengzhou University, 2013-2025) and externally validated it with 20 cases from Henan Cancer Hospital. Multivariate Cox regression identified TNM stage, CA125, Ki67, and primary tumor location as independent predictors of overall survival (OS). These factors were integrated into a nomogram and internally validated via bootstrap resampling. Compared to the TNM staging system, the nomogram demonstrated superior predictive performance, as indicated by lower Akaike (160.947 versus 168.746) and Bayesian Information Criterion values (169.391 versus 170.857). The bootstrap-corrected concordance index (C-index) for the nomogram was 0.800 (95% CI: 0.729-0.880), significantly outperforming the TNM system (0.653, 95% CI: 0.559-0.746; P = .001); the external validation C-index was 0.754 (95% CI: 0.638-0.870). Time-dependent C-index and calibration curves confirmed superior discriminative ability and accuracy, while decision curve analysis indicated clinical utility. Patients stratified as high-risk by the nomogram had significantly worse OS versus low-risk groups in both training (P < .0001) and validation cohorts (P = .02). This tool enables risk stratification to guide personalized HAS management.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress-driven LncRNA signature predicts cervical cancer prognosis and guides personalized immunotherapy: a multi-omics and functional validation study.","authors":"Jianchuan Hu, Zhongbing Qi, Shichuan Hu, Xianglin Xu, Yu Qin, Yao Zhang, Qingzhe Yang, Ping Cheng","doi":"10.1093/carcin/bgaf087","DOIUrl":"10.1093/carcin/bgaf087","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress is a key driver of tumor progression and therapeutic resistance. However, the prognostic role of ER stress-related long non-coding RNAs (lncRNAs) in cervical cancer has not been systematically elucidated. In this study, an ER stress-related lncRNA signature was constructed to evaluate patient prognosis and therapeutic responsiveness. Transcriptomic datasets derived from The Cancer Genome Atlas and the Genotype-Tissue Expression project were integrated, leading to the identification of 197 ER stress-associated differentially expressed genes and 1077 co-expressed lncRNAs. A prognostic 8-lncRNA model was developed using univariate/multivariate Cox regression and least absolute shrinkage and selection operator analysis. The model was validated by survival analysis (Kaplan-Meier and receiver operating characteristic curves), immune infiltration profiling (CIBERSORT and single-sample gene set enrichment analysis), and drug sensitivity analysis. Patients classified into the high-risk category showed significantly shorter overall survival (OS) (log-rank P < .001) and higher chemosensitivity to PI3K/mTOR inhibitors, whereas the low-risk group showed high immune activity (CD8+ T-cell infiltration and checkpoint expression) along with improved responsiveness to Wnt pathway inhibitors. The predictive capacity of the model (area under the curve, AUC: 0.806-0.856) exceeded that of conventional clinical parameters. Functional validation further revealed that LIPE-AS1, a representative high-risk lncRNA, promotes cervical cancer cell proliferation, migration, and invasion. These results introduce a novel ER stress-associated lncRNA signature with prognostic and therapeutic value, thus providing a potential basis for personalized immunotherapeutic and chemotherapeutic strategies in cervical cancer.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constitutive epidermal expression of osteopontin in osteopontin-null mice restores ultraviolet B-induced cutaneous squamous cell carcinomas to wild-type levels.","authors":"Chu-Fang Chou, Yun Huang, Jeremy B Foote, Yu-Hua Hsieh, Hui-Chien Kuo, David K Crossman, Michael R Crowley, Zorica Janjetovic, Andrej T Slominski, Craig Elmets, Pi-Ling Chang","doi":"10.1093/carcin/bgaf034","DOIUrl":"10.1093/carcin/bgaf034","url":null,"abstract":"<p><p>Studies of osteopontin (OPN)-null mice have supported the role of OPN as a critical factor in the promotion of skin tumorigenesis. OPN is a highly inducible integrin- and CD44-interacting acidic glycoprotein with pleiotropic functions. In various cancers, elevated levels of OPN from cancer and inflammatory cells are secreted into the microenvironment and the bloodstream. To determine whether OPN expressed by keratinocytes without contribution from activated resident and infiltrating inflammatory cells promotes cutaneous tumorigenesis, transgenic mice with constitutive epidermal expression of OPN in an OPN-null background (tg(K14-OPN)) were generated. In photocarcinogenesis studies, tumor multiplicity and the incidence of cutaneous squamous cell carcinoma (cSCC) were similar in the tg(K14-OPN) and wild-type (WT) mice. The incidence of cSCC was significantly higher in the WT than in OPN-null mice. This incidence did not reach significance in tg(K14-OPN) and OPN-null mice, likely due to fewer mice. Tg(K14-OPN) mice exhibited reduced keratinocyte apoptosis but not enhanced epidermal hyperplasia after ultraviolet B (UVB) exposure compared to OPN-null mice. Additionally, tg(K14-OPN) and OPN-null mice irradiated with long-term low-dose UVB had significantly lower numbers of mutated p53 keratinocytes than WT mice. RNA-sequencing data from the epidermis of acute UVB-irradiated tg(K14-OPN) versus OPN-null mice compared to UVB-irradiated WT versus OPN-null mice suggest the importance of inflammation, Wnt, integrin, and gonadotropin-releasing hormone receptor signaling in cutaneous tumorigenesis and implicates UVB irradiation and its induction of OPN in driving those pathways. In summary, the constitutive epidermal expression of OPN in OPN-null mice facilitates the development of cSCC comparable to WT mice.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774727","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":"Retraction of: TLR signaling-mediated differential histone modification at IL-10 and IL-12 promoter region leads to functional impairments in tumor-associated macrophages.","authors":"","doi":"10.1093/carcin/bgaf079","DOIUrl":"https://doi.org/10.1093/carcin/bgaf079","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"46 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A2AR-phospho-STAT1 (Y701)-HLA-E axis as a potential immune modulatory pathway in radiotherapy-resistant triple negative breast cancer.","authors":"Young Shin Ko, Hana Jin, So Eun Lee, Ju Yeong Won, Ju Heon Lee, Jong Sil Lee, Dong Chul Kim, Seung Pil Yun, Sang Won Park, Gyeong Won Lee, Hye Jung Kim","doi":"10.1093/carcin/bgaf069","DOIUrl":"10.1093/carcin/bgaf069","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) patients have lower survival rates and higher recurrence risks than non-TNBC patients. Moreover, radiotherapy-resistant TNBC (RT-R-TNBC) exhibits enhanced chemotherapy resistance and invasiveness. Therefore, there is a critical need for innovative treatments for RT-R-TNBC and TNBC patients. Our previous study indicated that NK cells exhibit reduced cytotoxicity against RT-R-TNBCs due to human leukocyte antigen class I histocompatibility antigen, alpha chain E (HLA-E) upregulation. Thus, this study aimed to identify the mechanism responsible for the upregulation of HLA-E and suggest potential therapeutic targets for overcoming the RT-resistance of TNBC. We found that HLA-E expression was significantly higher in TNBC tumor tissues than in normal epithelial tissues and non-TNBC tissues, correlating with A2AR levels. In addition, MDA-MB-231 (TNBC) and RT-R-MDA-MB-231 (RT-R-TNBC) showed an A2AR-dependent HLA-E overexpression. NK cell-mediated cytotoxicity against MDA-MB-231 and RT-R-MDA-MB-231 was reduced and restored by A2AR or STAT1 knockdown. Interestingly, STAT1 phosphorylation (Y701) by adenosine (ADO) aligned with the HLA-E expression pattern by ADO, and fludarabine, a STAT1 inhibitor, effectively reduced phospho-STAT1 (Y701) levels but not phospho-STAT1 (S727) levels. Fludarabine also inhibited ADO-induced HLA-E expression in MDA-MB-231 and RT-R-MDA-MB-231, including basal HLA-E expression in RT-R-MDA-MB-231. Additionally, fludarabine reduced tumor progression, lung metastasis, HLA-E expression, and phospho-STAT1 (Y701) in RT-R-MDA-MB-231-injected mice. Moreover, monalizumab, an NKG2A monoclonal antibody, significantly reduced tumor progression and lung metastasis with increased population of cytotoxic NK cells (CD25 + NK1.1+ and CD69 + NK1.1+) in the inguinal lymph nodes of RT-R-MDA-MB-231-injected mice. This study suggests that the A2AR-phospho-STAT1 (Y701)-HLA-E axis may serve as an alternative target for overcoming RT-resistance in TNBC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual activation of autophagy and mTOR by TFE3 fusions promotes tumorigenesis in rearranged renal cell carcinoma.","authors":"Ruina Wu, Xiaotong Wang, Miaomiao Tian, Xue Wei, Xuan Wang, Shengbing Ye, Rusong Zhang, Qiuyuan Xia, Ru Fang, Qiu Rao","doi":"10.1093/carcin/bgaf080","DOIUrl":"10.1093/carcin/bgaf080","url":null,"abstract":"<p><p>TFE3-rearranged renal cell carcinoma (TFE3-RCC), an aggressive kidney cancer predominantly affecting pediatric and young adult populations, is driven by Xp11.2 rearranged generating oncogenic TFE3 fusion proteins. Although these fusions define the disease, their mechanistic roles remain elusive. Here, lentiviral-mediated overexpression of PRCC-TFE3 or NONO-TFE3 in RCC models triggered nuclear rearranged fusion proteins and significantly accelerated tumor proliferation both in vitro and in vivo. Our integrated RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses mechanistically revealed that TFE3 fusions directly bind to promoters of lysosome and mTOR signaling pathway genes, leading to transcriptional activation of this pathway. Moreover, the fusions aberrantly escaped canonical mTOR signaling pathway regulation and paradoxically hyperactivated phospho-mTOR signaling. Importantly, dual inhibition of the autophagy and mTOR pathways synergistically suppressed tumor growth, exceeding the efficacy of single-agent treatments. These data demonstrate that co-targeting these TFE3-regulated pathways represents a promising therapeutic strategy for this intractable malignancy.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT-β-catenin signaling pathway.","authors":"","doi":"10.1093/carcin/bgaf088","DOIUrl":"https://doi.org/10.1093/carcin/bgaf088","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"46 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12697344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740789","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}