Zixiong Shen, Chuanlei Wang, Chunli Cao, Guangyi Wang, Zhiqin Li
{"title":"Gastroesophageal reflux disease as a risk factor for oral cavity and pharyngeal cancer: a Mendelian randomization study.","authors":"Zixiong Shen, Chuanlei Wang, Chunli Cao, Guangyi Wang, Zhiqin Li","doi":"10.1007/s12672-025-02105-1","DOIUrl":"10.1007/s12672-025-02105-1","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies have not clearly examined the impact of gastroesophageal reflux disease (GERD) on the risk of oral cavity and pharyngeal cancer (OCPC). To provide more evidence to elucidate this issue, we used Mendelian randomization (MR) to analyze the causal effect of GERD on OCPC and its subtypes.</p><p><strong>Methods: </strong>We obtained the summary data of genome-wide association studies (GWAS) of European ancestry to perform MR analysis. GERD was considered the exposure, and OCPC (subtypes include oral cavity cancer (OCC) and oropharynx cancer (OPC)) was defined as the outcome. We aimed to investigate whether GERD has a causal effect on OCPC. We then attempted to obtain more accurate causal estimates by correcting for potential confounders such as smoking behavior, drinking behavior, body mass index (BMI), and type 2 diabetes (T2D). We also performed extensive sensitivity analyses to assess the robustness of the primary analysis results.</p><p><strong>Results: </strong>Univariate MR analysis showed that GERD had a positive causal effect on OCPC (IVW: discovery, OR = 2.09 (95% CI 1.30-3.37), P = 0.0023; validation, OR = 1.90 (95% CI 1.26-2.87), P = 0.0020) and OCC (IVW: discovery, OR = 2.01 (95% CI: 1.21-3.33), P = 0.0066; validation, OR = 2.60 (95% CI 1.47-4.59), P = 0.0010). Although GERD increased the risk of OPC, this effect was statistically significant only in the discovery analysis (IVW: discovery, OR = 2.30 (95% CI 1.08-4.89), P = 0.0307; validation, OR = 1.15 (95% CI 0.67-1.97), P = 0.6199), the causal direction remained consistent. After adjusting for smoking, alcohol consumption, BMI, and T2D in multivariate analysis, the results remained largely consistent.</p><p><strong>Conclusions: </strong>Our study showed that GERD significantly increased the overall risk of OCPC, and similar results were found for its subtype OCC. This causal effect appears to be independent of cigarette use, drinking habits, BMI, and T2D. However, evidence for a causal effect of GERD on OPC is limited, and further research is expected to extend this finding. Future studies should explore the specific biological mechanisms through which GERD increases OCPC risk.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"353"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656334","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}
Qier Li, Jingzhi Wang, Qingqing Liu, Min Gan, Jianing Yan, Xuan Yu, Yongfu Shao
{"title":"Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration.","authors":"Qier Li, Jingzhi Wang, Qingqing Liu, Min Gan, Jianing Yan, Xuan Yu, Yongfu Shao","doi":"10.1007/s12672-025-02085-2","DOIUrl":"10.1007/s12672-025-02085-2","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer has high incidence and mortality rates. The signal transducer and activator of transcription (STAT) family plays vital roles in the tumorigenesis and development of colorectal cancer. The expression, prognostic value, and immune function of the STAT family are becoming much more clearly.</p><p><strong>Methods: </strong>Our study collected data from several public data portals such as TCGA (644 samples) and GTEx database (308 samples) and clinical samples (30 samples, China). Then we systematically assessed the expression level and prognostic value of the STAT family in colorectal cancer samples. Moreover, the immune function and immune infiltration levels of prognosis-related STAT members were explored via single cell RNA-seq and spatial transcriptomics technology data. Several useful portals and tools have been utilized such as CancerSEA and TISIDB in single-cell analysis, CBio Cancer Genomics in multidimensional alterations, MethSurv in DNA methylation, and related R packages.</p><p><strong>Results: </strong>Our study found that STAT3 and STAT5B were significantly lower in colorectal cancer via multi-omics (P < 0.001). Higher STAT3 and STAT5B level were correlated with better future outcome. Nomograms were developed to predict the distal survival time (C-index = 0.724). The functions of STAT3 and STAT5B are associated with inflammation, the JAK/STAT pathway and the immune response. The major cell types of colorectal cancer were CD4Tconv, CD8T, CD8Tex, Tprolif, Treg and STAT3 and STAT5B widely expressed in these cells. STAT3 and STAT5B both correlated with CD244 and KDR for immune checkpoints.</p><p><strong>Conclusion: </strong>STAT3 and STAT5B are downregulated in colorectal cancer and have great potential as prognostic biomarkers and novel immunotherapy targets.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"343"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656333","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":"Nomogram construction for overall survival in breast angiosarcoma based on clinicopathological features: a population-based cohort study.","authors":"Peikai Ding, Luxiao Zhang, Shengbin Pei, Zheng Qu, Xiangyi Kong, Zhongzhao Wang, Jing Wang, Yi Fang","doi":"10.1007/s12672-025-02118-w","DOIUrl":"10.1007/s12672-025-02118-w","url":null,"abstract":"<p><strong>Background: </strong>Breast angiosarcoma (BAS) is a rare, aggressive malignancy with a poor prognosis, often challenging to assess due to its unique biology. This study aimed to develop a nomogram to predict 3- and 5-year overall survival (OS) for BAS patients using key clinicopathological factors.</p><p><strong>Methods: </strong>Data from 450 BAS patients diagnosed between 2000 and 2021 were extracted from SEER database. Key variables, including age, tumor size, tumor grade, and distant metastasis status, were identified through univariate and multivariate Cox regression analyses. These factors were incorporated into a nomogram for OS prediction. The model was validated internally and externally using the concordance index (C-index), calibration curves, and decision curve analysis (DCA) to assess its predictive accuracy and clinical utility.</p><p><strong>Results: </strong>The nomogram demonstrated good predictive accuracy, with a C-index of 0.68 in the training set and 0.72 in the test set. ROC analysis indicated strong short-term predictive power, with AUC values of 0.81 and 0.75 for 1-year survival in the training and test sets, respectively, though predictive performance declined over time. DCA showed substantial clinical benefit for 12-month predictions, which diminished over longer time frames. The model effectively distinguished high-risk BAS patients and provided individualized survival estimates, supporting its potential use in clinical decision-making.</p><p><strong>Conclusion: </strong>This study presents the first BAS nomogram for OS prediction, showing robust short-term accuracy. The long-term utility is limited by heterogeneity and sample size, highlighting the need for external validation to confirm generalizability and clinical applicability.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"351"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656260","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":"Disulfidptosis-based molecular clustering and prognostic signatures predict patient survival and the immune landscape in patients with colon cancer.","authors":"Liang Wen, Yongli Ma, Jinghui Li, Dengzhuo Chen, Chengzhi Huang, Ping Wang, Suqi Wen, Gexin Wen, Jizhen Guo, Guosheng Zhang, Junjiang Wang, Xueqing Yao","doi":"10.1007/s12672-025-02142-w","DOIUrl":"10.1007/s12672-025-02142-w","url":null,"abstract":"<p><strong>Introduction: </strong>Disulfidptosis is a unique type of programmed cell death that is distinct from previously known forms of cell death, such as pyroptosis, apoptosis, and necroptosis. Researchers have studied the significance of many forms of cell death in various diseases, particularly malignant tumors, in great detail in recent years. Therefore, how disulfidptosis affects colon cancer and how it functions in the immune system are unknown.</p><p><strong>Methods: </strong>Disulfidptosis-related gene (DRG) expression information was obtained from the TCGA-COAD cohort. Patients were categorized into two DRG groups using consensus cluster analysis, and the disulfidptosis-related differentially expressed genes (DRDEGs) were subsequently identified by differential analysis of the two clusters. Univariate Cox regression analysis of the DRDEGs was used to identify prognosis-related DEGs (PRDEGs). The screened PRDEGs were then subjected to LASSO-Cox regression analysis to determine the prognostic model on the basis of ten genes. Immunohistochemistry was used to verify the expression and prognostic value of marker genes.</p><p><strong>Results: </strong>In the two DRG clusters, the characteristics of the tumor microenvironment (TME) significantly differed by the TME scores and infiltration levels of 23 human immune cell subpopulations. Prognostically meaningful risk scores were found, with a greater chance of mortality (p = 4.4e-7) for patients in the high-risk category. Furthermore, notable differences in TME scores, immune cell infiltration, and immune checkpoint expression were detected among the risk categories. The ROC curves revealed that the nomogram's 1-, 2-, and 3-year AUCs were 0.75, 0.76, and 0.77, respectively, demonstrating the superior predictive capacity of the nomogram. Immunohistochemistry revealed that patients with high FABP4 and low ADAM8 and FSTL3 expressions had a better prognosis.</p><p><strong>Conclusion: </strong>The prognostic features based on 10 PRDEGs performed well in predicting survival, TME status, and response to immunity in COAD patients, helping provide personalized immunotherapy strategies for patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"354"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656332","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":"Serum CDC42 level change during abiraterone plus prednisone treatment and its association with prognosis in metastatic castration-resistant prostate cancer patients.","authors":"Yong Ma, Zhihua Cao, Jiacheng Zhang, Xu Zhu, Zhonghao Zhao, Jinguo Xiong","doi":"10.1007/s12672-025-02130-0","DOIUrl":"10.1007/s12672-025-02130-0","url":null,"abstract":"<p><strong>Objective: </strong>Cell division cycle 42 (CDC42) regulates prostate cancer growth and metastasis. This study aimed to evaluate the change in serum CDC42 during treatment and its association with the clinical features and prognosis in abiraterone plus prednisone treated metastatic castration-resistant prostate cancer (mCRPC) patients.</p><p><strong>Methods: </strong>Seventy-two mCRPC patients who underwent abiraterone plus prednisone therapy were included in this retrospective study, followed by the serum CDC42 level determination at baseline and month 2 (M2). Additionally, serum CDC42 was detected in thirty age-matched healthy controls (HCs).</p><p><strong>Results: </strong>The CDC42 level was higher in mCRPC patients versus HCs [median (interquartile range): 1012.5 (655.8-1671.3) versus 606.0 (392.0-1007.0) pg/mL] (P < 0.001). Meanwhile, the CDC42 level was associated with lymph node metastasis (P = 0.041) and visceral metastasis (P = 0.005), but not other clinical characteristics (P > 0.050) in mCRPC patients. Additionally, the CDC42 level was decreased after 2-month treatment (P < 0.001). Inspiringly, shorter radiographic progression-free survival (rPFS) was observed in mCRPC patients with CDC42 > 1000 pg/mL than in those with CDC42 ≤ 1000 pg/mL at baseline (P = 0.035). Furthermore, shorter rPFS (P = 0.002) and overall survival (P = 0.043) were discovered in mCRPC patients with CDC42 > 1000 pg/mL than in those with CDC42 ≤ 1000 pg/mL at M2. More importantly, CDC42 at M2 (> 1000 vs. ≤ 1000 pg/mL) was independently associated with shorter rPFS in mCRPC patients (P = 0.035, hazard ratio = 2.203).</p><p><strong>Conclusion: </strong>The serum CDC42 level associates with LNM, visceral metastasis, and worse prognosis in mCRPC patients underwent abiraterone plus prednisone therapy. However, future prospective, large-scale, and controlled studies are needed for validation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"355"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656262","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}
Lin Guo, Jia Zhang, Yuqiang Li, Yuehong Gao, Jiali Huang, Mengru Liu, Jing Li, Wenshu Chai, Yubin Li
{"title":"3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis.","authors":"Lin Guo, Jia Zhang, Yuqiang Li, Yuehong Gao, Jiali Huang, Mengru Liu, Jing Li, Wenshu Chai, Yubin Li","doi":"10.1007/s12672-025-02096-z","DOIUrl":"10.1007/s12672-025-02096-z","url":null,"abstract":"<p><p>Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. In lung cancer, AHR activation stimulates cancer cell proliferation and promotes tissue invasion and metastasis, and targeting the AHR pathway is an effective way to prevent and treat lung cancer. In lung cancer, AHR binds to the NRF2 promoter region to promote carcinogenesis, but treatment research based on AHR/NRF2 pathway is insufficient. 3,3'-diindolylmethane (DIM), an active phytochemical derivative extracted from cruciferous vegetables, is a modulator of AHR. In this study, We investigated the medicinal value of DIM in NSCLC (non-small cell lung cancer) by in vivo and in vitro experiments and explored the underlying mechanisms. In vitro studies showed that DIM inhibited the viability of NSCLC and induced apoptosis and cycle arrest in cancer cells. DIM inhibited the migration and invasion of NSCLC cells by reversing the epithelial-mesenchymal transition. DIM induced ferroptosis in NSCLC cells; increased cellular Fe<sup>2+</sup>, ROS (reactive oxygen species), and MDA; decreased cellular GSH, AHR, NRF2, and GPX4; and disrupted the mitochondrial membrane potential. The effect of DIM-induced ferroptosis can be reversed by the AHR receptor antagonist CH-223191, ferroptosis inhibitor Fer-1, and ROS scavenger NAC. Overexpression of NRF2 reversed DIM-induced ferroptosis. Identical results were obtained in a nude mouse xenograft model. In summary, we have confirmed that DIM has significant potential in the treatment of non-small cell lung cancer. DIM induces cancer cell ferroptosis through the AHR/NRF2/GPX4 axis. These findings provide experimental basis for DIM treatment and future clinical research in non-small cell lung cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"344"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656329","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}
Lei Shi, Huimei Wang, Yongxiao Sun, Na Xu, Aiyue Pei, Nan Zhang
{"title":"Development and validation of a disulfidptosis-related prognostic model for colorectal cancer using multi-omics analysis.","authors":"Lei Shi, Huimei Wang, Yongxiao Sun, Na Xu, Aiyue Pei, Nan Zhang","doi":"10.1007/s12672-025-02055-8","DOIUrl":"10.1007/s12672-025-02055-8","url":null,"abstract":"<p><p>This study aims to integrate multi-omic and clinical data concerning disulfidptosis-related genes (DRGs) to facilitate molecular typing and prognosis in colorectal cancer (CRC). Public databases provided CRC transcriptome and clinical data, enabling differential expression, genomic analyses, pathway enrichment, survival analysis, and subtyping based on the expression levels of 15 DRGs identified in published studies. Differentially expressed genes (DEGs) between subtypes were identified to create a disulfidptosis prognostic model using LASSO and Cox regression analyses. This model was evaluated by comparing risk scores, survival curves, cellular infiltration, and drug sensitivity between high- and low-risk groups. Analyses revealed differential expression, mutations, and copy number variations (CNV) in DRGs in CRC. Survival analysis demonstrated significant prognostic differences among DRG expression subtypes. GSVA and ssGSEA highlighted DRGs' regulatory roles in CRC. DEGs identified between DRG expression subtypes led to the classification into subtypes A and B. A disulfidptosis prognostic model, including genes VSIG4, SCG2, INHBB, DDC, CXCL13, KLK10, CXCL10, and CCL11A, was developed to stratify patients into high- and low-risk groups. This model displayed strong predictive capability (AUC = 0.700) and calibration. The risk score was also strongly associated with immune cell infiltration, stromal cell score, and stem cell index in the CRC tumor microenvironment. Drug sensitivity analysis indicated that high-risk samples were more responsive to most medications. We established a robust disulfidptosis prognostic model for CRC through comprehensive multi-omics analysis. Our findings provide valuable insights into the role of DRGs in CRC progression and disease management, presenting an important resource for further research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"338"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647550","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}
Yang Wu, Tian Li, Runbing Zhang, Tingting Shi, Shunna Wang, Lingling Zhu, Yani Zhang, Xiaofeng Zheng, Xiaohui Yu, Jiucong Zhang
{"title":"Establishment of nomogram of early death in elderly pancreatic cancer patients with liver metastasis.","authors":"Yang Wu, Tian Li, Runbing Zhang, Tingting Shi, Shunna Wang, Lingling Zhu, Yani Zhang, Xiaofeng Zheng, Xiaohui Yu, Jiucong Zhang","doi":"10.1007/s12672-025-02059-4","DOIUrl":"10.1007/s12672-025-02059-4","url":null,"abstract":"<p><strong>Background: </strong>Many elderly patients with pancreatic cancer (PC) often have liver metastasis (LM), and these patients often have poor prognosis and early death (ED). However, few models can accurately predict ED from elderly PC patients with LM. Therefore, we aim to create nomograms to predict ED in elderly PC patients with LM.</p><p><strong>Methods: </strong>All elderly (≥ 60 years old) PC patients with LM from 2010 to 2020 were downloaded from the Surveillance, Epidemiology, and End Result (SEER) database according to the admission criteria. The included data was randomly divided into the training set and the validation set, with a ratio of 7:3. The risk factors for ED in elderly PC patients with LM were determined by univariate and multivariate logistic regression methods, and a nomogram model was established. Lastly, the nomogram is verified by the receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve, and decision curve analysis (DCA).</p><p><strong>Results: </strong>A total of 1,424 elderly PC patients with LM were randomly divided into training set (n = 996) and validation set (n = 428) based on the ratio of 7:3. The independent prognostic factors for ED include T stage, N stage, surgery, chemotherapy, lung metastasis, and other metastases. These variables were used to create nomograms, where the AUC of the training set and the validation set were 0.83 (95% CI 0.80-0.85) and 0.81 (95% CI 0.77-0.85), respectively. Furthermore, the calibration curve shows that the predicted ED is in good agreement with the actual value. DCA also shows good clinical application value.</p><p><strong>Conclusions: </strong>The developed nomogram can be used to predict the specific probability of ED in elderly PC patients with LM, which is useful in guiding the early prevention and treatment decision-making of this group of people.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"333"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647556","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}
Zihe Liu, Sheng Chang, Shouguo Chen, Rong Gu, Shaoyong Guo
{"title":"A novel prognostic signature based on m5C‑related LncRNAs and its immunological characteristics in colon adenocarcinoma.","authors":"Zihe Liu, Sheng Chang, Shouguo Chen, Rong Gu, Shaoyong Guo","doi":"10.1007/s12672-025-02081-6","DOIUrl":"10.1007/s12672-025-02081-6","url":null,"abstract":"<p><strong>Background: </strong>Colon adenocarcinoma (COAD) has high mortality rates due to frequent resistance to treatment. 5-methylcytosine (m5C) is a crucial epigenetic modification of RNA, closely associated with tumorigenesis in various cancers. This study focuses on developing an m5C-related long non-coding RNA (lncRNA) signature to predict prognosis and explore potential therapeutic targets.</p><p><strong>Methods: </strong>Using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we analyzed 18 m5C regulatory genes and their associated lncRNAs in COAD samples. Prognostic lncRNAs were identified through univariate Cox regression, and a risk model was constructed through LASSO regression analyses. Kaplan-Meier survival and receiver operating characteristic analyses were employed to validate the prognostic ability of the signature. Additionally, functional enrichment and immune infiltration analyses were conducted to investigate underlying biological pathways and immune characteristics of the risk groups. Tumor mutation burden and drug sensitivity analyses were also performed. Functional validation of NR2F2-AS1 was conducted through in vitro experiments.</p><p><strong>Results: </strong>We established a risk score signature comprising six lncRNAs associated with m5C regulators. Patients were classified into high- and low-risk groups based on the median risk score. This prognostic signature demonstrated significant accuracy and was independent of other clinical features. Immune cell infiltration analysis revealed correlations between the risk signature and various immune cell subtypes. Drug sensitivity analysis indicated the potential therapeutic value of our prognostic signature. Functional experiments confirmed that NR2F2-AS1 acts as a risk factor in the proliferation of colon cancer cells.</p><p><strong>Conclusions: </strong>The m5C-related lncRNA signature serves as a reliable prognostic indicator for colon adenocarcinoma and provides new insights into the tumor immune microenvironment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"332"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647628","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}