Identiﬁcation of a coagulation-related classiﬁcation and signature that predict disease heterogeneity for colorectal cancer and pan-cancer patients

Sep 23, 2026

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In colorectal cancer (CRC) and broader pan-cancer cohorts, increased coagulation is linked to tumor progression, yet coagulation-related genes have not been fully characterized. This study identified coagulation-related subtypes (CRSs) and evaluated a corresponding prognostic risk score for disease heterogeneity. CRC datasets from The Cancer Genome Atlas were used to derive CRSs and signatures, then validated across independent and pan-cancer cohorts. Immune features, drug sensitivity, and an overall-survival nomogram supported the clinical and biological relevance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Background

Methods

Results

Conclusions

Introduction

TYPE Original Research PUBLISHED 24 July 2025 DOI 10.3389/fimmu.2025.1572701 OPEN ACCESS EDITED BY Zhiwen Luo, Fudan University, China REVIEWED BY Sambhavi Animesh, Harvard Medical School, United States Saleh Alsaleh, Queen Mary University of London, United Kingdom *CORRESPONDENCE Aiwen Wu [drwuaw@sina.com](drwuaw@sina.com) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 07 February 2025 ACCEPTED 07 July 2025 PUBLISHED 24 July 2025 CITATION Pei J, Gao Y, Xing B, Chen Y and Wu A (2025) Identiﬁcation of a coagulation-related classiﬁcation and signature that predict disease heterogeneity for colorectal cancer and pan-cancer patients. Front. Immunol. 16:1572701 . doi: 10.3389/fimmu.2025.1572701 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) and the copyright owner(s) 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. Identiﬁcation of a coagulationrelated classiﬁcation and signature that predict disease heterogeneity for colorectal cancer and pan-cancer patients Junpeng Pei 1,2†, Yuye Gao 1,2†, Baojian Xing3†, Yongjiu Chen 1,2 and Aiwen Wu 1,2* 1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China, 2 Beijing Key Laboratory of Carcinogenesis and Translational Research, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China, 3 Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China 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 conﬁr med the bioinformatics predictions regarding TIMP1 ’s role in CRC progression. Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Conclusions: A coagulation-based classiﬁer effectively categorizes CRC and potentially other cancers, interacting signiﬁcantly with the immune microenvironment to inﬂuence disease progression and treatme

FAQs

What gap does the study address about coagulation in colorectal cancer?

The study targets the limited understanding of how coagulation-related genes specifically contribute to colorectal cancer biology and patient heterogeneity.

How were coagulation-related subtypes (CRSs) identified and validated?

CRSs were derived from CRC data using nonnegative matrix factorization and validated across an independent dataset (GSE39582) and pan-cancer datasets.

What is the coagulation-related risk signature and what does it predict?

The risk signature was built from F2RL2, GP1BA, MMP10, GP1BA, and TIMP1, stratifying CRC patients by outcomes and aligning with differences in immune infiltration and therapeutic response.

Sep 23, 2026

Uploaded by Mabel