Li Qiusheng, Wang Changjing, Wang Guiying
Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Department of Gastrointestinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Sci Rep. 2025 Aug 26;15(1):31382. doi: 10.1038/s41598-025-17230-8.
COL4A1, a key component of the basement membrane, has been increasingly implicated in tumor progression, yet its role in colon cancer remains incompletely understood. In this study, we conducted a comprehensive integrative analysis using transcriptomic data from the TCGA-COAD cohort, combined with functional validation in colon cancer cell lines. Gene set enrichment analysis (GSEA) revealed that high COL4A1 expression was associated with oncogenic pathways including epithelial-mesenchymal transition (EMT), KRAS signaling, and inflammatory responses. Immune infiltration analysis indicated that COL4A1 expression negatively correlated with CD8 T cell infiltration but positively correlated with macrophage subtypes. Immunophenoscore (IPS) analysis further revealed that tumors with high COL4A1 expression exhibited significantly higher IPS values, suggesting altered immunogenicity. Functional assays demonstrated that COL4A1 knockdown reduced cell proliferation, migration, and invasion in vitro. Co-expression analysis of EMT markers showed strong positive correlations between COL4A1 and mesenchymal genes such as VIM, ZEB1, SNAI1, and FN1, supporting its role in EMT-like phenotypes. Collectively, our findings suggest that COL4A1 may serve as a prognostic biomarker and contributor to tumor progression and immune remodeling in colon cancer.
COL4A1是基底膜的关键组成部分，越来越多地被认为与肿瘤进展有关，但其在结肠癌中的作用仍未完全明确。在本研究中，我们使用来自TCGA-COAD队列的转录组数据进行了全面的综合分析，并结合了结肠癌细胞系中的功能验证。基因集富集分析（GSEA）显示，COL4A1高表达与致癌途径相关，包括上皮-间质转化（EMT）、KRAS信号传导和炎症反应。免疫浸润分析表明，COL4A1表达与CD8 T细胞浸润呈负相关，但与巨噬细胞亚型呈正相关。免疫表型评分（IPS）分析进一步显示，COL4A1高表达的肿瘤表现出明显更高的IPS值，表明免疫原性改变。功能试验表明，COL4A1敲低可降低体外细胞增殖、迁移和侵袭。EMT标志物的共表达分析显示，COL4A1与VIM、ZEB1、SNAI1和FN1等间充质基因之间存在强正相关，支持其在类似EMT表型中的作用。总体而言，我们的研究结果表明，COL4A1可能作为结肠癌预后的生物标志物，并促进肿瘤进展和免疫重塑。
