ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1572701
This article is part of the Research TopicIntegrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and OncologyView all 31 articles
Identification of a coagulation-related classification and signature that predict disease heterogeneity for colorectal cancer and pan-cancer patients
Provisionally accepted
- 1Beijing Cancer Hospital, Peking University, Beijing, China
- 2Sheng Jing Hospital Affiliated, China Medical University, Shenyang, Liaoning Province, China
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Background While increased coagulation is linked to cancer progression, the specific roles of coagulation-related genes in colorectal cancer (CRC) have not been extensively studied. This research identified coagulation-related subtypes (CRSs) and evaluated a coagulation-related risk score for its prognostic value in CRC.Methods CRC dataset from The Cancer Genome Atlas was analyzed to identify CRSs using nonnegative matrix factorization, which was validated across GSE39582 and pan-cancer datasets. A list of 285 coagulation-related genes was used to develop a risk signature via least absolute shrinkage and selection operator and multivariate Cox regression. We also assessed immune characteristics and treatment responses using single-sample gene set enrichment analysis, Tumor Immune Dysfunction and Exclusion, and immunophenoscore, and constructed an overall survival-related nomogram.Results CRS analysis categorized pan-cancers, including CRC, into three clusters: C1 with poor immune infiltration but better prognosis, C2 with high immune activity and prolonged survival, and C3 marked by dense immunosuppressive cells correlating with poor outcomes. Drug sensitivity analysis showed distinct responses across CRSs, influencing treatment choices. We developed a coagulation-related risk score based on F2RL2, GP1BA, MMP10, and TIMP1, which stratified CRC patients by outcome and correlated with distinct patterns of immune infiltration and therapeutic response. A validated nomogram incorporating age, TNM stage, and risk score accurately predicted overall survival, while experimental validations confirmed the bioinformatics predictions regarding TIMP1's role in CRC progression.Conclusions A coagulation-based classifier effectively categorizes CRC and potentially other cancers, interacting significantly with the immune microenvironment to influence disease progression and treatment responsiveness. This approach offers valuable insights for personalized cancer therapy.
Keywords: coagulation, clustering, colorectal cancer, Precision treatment, Tumor Microenvironment
Received: 07 Feb 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Pei, Gao, Xing, Chen and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Aiwen Wu, Beijing Cancer Hospital, Peking University, Beijing, China
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