Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis
Colorectal cancer (CRC) represents a significant global health challenge. Although telomere maintenance plays a crucial role in tumorigenesis, the prognostic value and immunotherapeutic relevance of telomere maintenance genes (TMGs) in CRC remain poorly understood. In this study, relevant data were...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2025-07-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/12053 |
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| author | Zhikai Wang Chunyan Zhao Yifen Huang Chong Li |
| author_facet | Zhikai Wang Chunyan Zhao Yifen Huang Chong Li |
| author_sort | Zhikai Wang |
| collection | DOAJ |
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Colorectal cancer (CRC) represents a significant global health challenge. Although telomere maintenance plays a crucial role in tumorigenesis, the prognostic value and immunotherapeutic relevance of telomere maintenance genes (TMGs) in CRC remain poorly understood. In this study, relevant data were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. TMG scores were calculated using the single-sample gene set enrichment analysis (ssGSEA) method, and TMGs associated with prognosis were subsequently identified. TCGA-CRC samples were classified into subtypes via consensus clustering (ConsensusClusterPlus). A risk prediction model was then constructed using univariate and Lasso Cox regression analyses. Survival analysis was performed using Kaplan–Meier curves generated with the survival package. Key genes were validated in vitro using cellular models. Immune cell infiltration was evaluated through ssGSEA, TIMER, and MCP-Counter tools, and chemotherapy responses were predicted using the pRRophetic package. From 28 prognosis-related TMGs, two distinct CRC subtypes were established, with subtype C1 demonstrating more favorable clinical outcomes. Additionally, a risk model incorporating seven TMG-related genes (CDC25C, CXCL1, RTL8C, FABP4, ITLN1, MUC12, and ERI1) was developed for CRC prognosis. Differential mRNA expression levels of these genes were confirmed between CRC cell lines and normal control cells. Furthermore, silencing MUC12 suppressed CRC cell migration and invasion in vitro. Importantly, CRC patients classified as low-risk exhibited superior responses to immunotherapy, whereas high-risk patients showed increased sensitivity to conventional anti-cancer treatments. This study represents the first systematic evaluation of TMGs in CRC prognosis and immunotherapy, providing novel insights that could inform personalized therapeutic strategies.
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| format | Article |
| id | doaj-art-d94d14e6de6a4e7c942603dcf33d69be |
| institution | Kabale University |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj-art-d94d14e6de6a4e7c942603dcf33d69be2025-08-20T03:50:00ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2025-07-0110.17305/bb.2025.12053Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosisZhikai Wang0Chunyan Zhao1Yifen Huang2Chong Li3Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, Zhengzhou, ChinaDepartment of Oncology, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, ChinaOutpatient Department, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Oncology, The Affiliated Dazu's Hospital of Chongqing Medical University, Chongqing, China Colorectal cancer (CRC) represents a significant global health challenge. Although telomere maintenance plays a crucial role in tumorigenesis, the prognostic value and immunotherapeutic relevance of telomere maintenance genes (TMGs) in CRC remain poorly understood. In this study, relevant data were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. TMG scores were calculated using the single-sample gene set enrichment analysis (ssGSEA) method, and TMGs associated with prognosis were subsequently identified. TCGA-CRC samples were classified into subtypes via consensus clustering (ConsensusClusterPlus). A risk prediction model was then constructed using univariate and Lasso Cox regression analyses. Survival analysis was performed using Kaplan–Meier curves generated with the survival package. Key genes were validated in vitro using cellular models. Immune cell infiltration was evaluated through ssGSEA, TIMER, and MCP-Counter tools, and chemotherapy responses were predicted using the pRRophetic package. From 28 prognosis-related TMGs, two distinct CRC subtypes were established, with subtype C1 demonstrating more favorable clinical outcomes. Additionally, a risk model incorporating seven TMG-related genes (CDC25C, CXCL1, RTL8C, FABP4, ITLN1, MUC12, and ERI1) was developed for CRC prognosis. Differential mRNA expression levels of these genes were confirmed between CRC cell lines and normal control cells. Furthermore, silencing MUC12 suppressed CRC cell migration and invasion in vitro. Importantly, CRC patients classified as low-risk exhibited superior responses to immunotherapy, whereas high-risk patients showed increased sensitivity to conventional anti-cancer treatments. This study represents the first systematic evaluation of TMGs in CRC prognosis and immunotherapy, providing novel insights that could inform personalized therapeutic strategies. https://www.bjbms.org/ojs/index.php/bjbms/article/view/12053ImmunotherapyRisk modelPrognostic signatureTelomere maintenance geneColorectal cancer |
| spellingShingle | Zhikai Wang Chunyan Zhao Yifen Huang Chong Li Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis Biomolecules & Biomedicine Immunotherapy Risk model Prognostic signature Telomere maintenance gene Colorectal cancer |
| title | Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| title_full | Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| title_fullStr | Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| title_full_unstemmed | Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| title_short | Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| title_sort | role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis |
| topic | Immunotherapy Risk model Prognostic signature Telomere maintenance gene Colorectal cancer |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/12053 |
| work_keys_str_mv | AT zhikaiwang roleoftelomeremaintenancegenesasapredictivebiomarkerforcolorectalcancerimmunotherapyresponseandprognosis AT chunyanzhao roleoftelomeremaintenancegenesasapredictivebiomarkerforcolorectalcancerimmunotherapyresponseandprognosis AT yifenhuang roleoftelomeremaintenancegenesasapredictivebiomarkerforcolorectalcancerimmunotherapyresponseandprognosis AT chongli roleoftelomeremaintenancegenesasapredictivebiomarkerforcolorectalcancerimmunotherapyresponseandprognosis |