ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Prognostic Value and Experimental Validation of Atherosclerosis-Derived Pathogenic Genes in Colorectal Cancer
Provisionally accepted
Yuqing Li1
Jinhong Wei1
Yuanyuan Xu1
Zhenyu Wu2Saiqi He1
YuHang Zhu3
Wen Ni1Di Zhang1Huiya Xu1Chuanjie Zhang1Aijun Zhou1
Tong Shen4*Jianming Li1,4*- 1Sun Yat-sen Memorial Hospital, Guangzhou, China
- 2Affiliated Hospital of Zunyi Medical University, Zunyi, China
- 3Key Laboratory of Brain Function and Brain Disease Prevention and Treatment of Guizhou, Zunyi, China
- 4Soochow University Medical School, Suzhou, China
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Objectives: Colorectal cancer (CRC) and atherosclerosis (AS) share pathological phenotypes and clinical links, but their shared pathogenic mechanisms are unclear. This study aimed to identify shared genetic drivers, construct a CRC risk model using AS-related genes, and validate expression via multi-omics. Methods: Transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed. Core gene modules associated with CRC and AS were screened using weighted gene co-expression network analysis and differentially expressed genes with significant expression differences between CRC tissues and normal tissues were identified through differential analysis. The intersection of these three sets of genes was taken to determine the overlapping genes..A prognostic model with 6 key genes (CDC25C, HMMR, KPNA2, PRR11, PALB2 and TKT) was built via univariate Cox and least absolute shrinkage and selection operator analyses. High/low-risk groups underwent Gene Set Enrichment Analysis (GSEA), immune infiltration, and immune checkpoint analyses. Multi-omics characterized gene expression/localization, validated by reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. Results: The model showed reliable predictive performance. Low-risk groups had enriched activated dendritic cells and follicular helper T cells; high-risk groups featured memory B cells and resting mast cells. Most genes overexpressed in lesions, except PRR11 (higher in normal tissues). Experiments confirmed HMMR/PALB2 overexpression in CRC and three AS genes elevated in AS lesions. Conclusion: A CRC risk model based on 6 AS-related genes was developed, identifying 3 novel AS genes. It highlights shared genetic factors, offering prognostic biomarkers for both diseases and insights into their interconnected mechanisms.
Keywords: colorectal cancer, Atherosclerosis, bioinformatics, Risk model, tumor immunemicroenvironment
Received: 19 Oct 2025; Accepted: 16 Dec 2025.
Copyright: © 2025 Li, Wei, Xu, Wu, He, Zhu, Ni, Zhang, Xu, Zhang, Zhou, Shen and Li. 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:
Tong Shen
Jianming Li
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