Prognostic value and experimental validation of atherosclerosis-derived pathogenic genes in colorectal cancer

作者：Yuqing Li, Jinhong Wei, Yuanyuan Xu, Zhenyu Wu, Saiqi He, Yuhang Zhu, Wen Ni, Di Zhang, Huiya Xu, Chuanjie Zhang, Aijun Zhou, Tong Shen, Jin Li · 发表于：Frontiers in Oncology · 年份：2026 · DOI：10.3389/fonc.2025.1728087 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Lipids, and Metabolism、Atherosclerosis and Cardiovascular Diseases

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 PR...