Exploration of effective biomarkers and infiltrating immune cells in metastatic colorectal cancer based on bioinformatics analysis

Abstract

Abstract Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally and represents the second leading cause of cancer-related mortality worldwide. Metastatic colorectal cancer (mCRC) is clinically classified as an advanced-stage malignancy, characterized by therapeutic resistance and substantially diminished survival outcomes. The 5-year survival rate for mCRC is significantly lower than that for early-stage CRC. A multi-dimensional computational framework was implemented to dissect CRC transcriptomics. Gene expression profiles were systematically acquired from TCGA and GEO repositories. A series of data were then analyzed using ssGSEA algorithm, xCell algorithm, edgeR, limma, DAVID enrichment analysis, CytoHubba, ROC logistic regression and correlation analysis. Immune cell infiltration analysis revealed 7 tumor-infiltrating immune cell subtypes exhibiting significant abundance disparities between metastatic and non-metastatic colorectal cancer cohorts. Further integrative analysis identified 28 immune-related metastatic colorectal cancer differentially expressed genes (ICDEGs) in metastatic lesions. Through comprehensive analysis, 9 pivotal hub genes (AGTR1, CD86, CMKLR1, FGF1, FYN, IL10RA, INHBA, TNFSF13B, and VEGFC) were successfully identified. Notably, AGTR1, CD86, CMKLR1 and TNFSF13B genes have been rarely reported in mCRC. Furthermore, our correlation studies revealed significant inverse relationships between epithelial cells and three specific genes: TNFSF13B, CD86, and IL10RA. The identified 9 hub genes demonstrate significant potential as reliable diagnostic biomarkers for mCRC. Moreover, these molecular markers may contribute to disease pathogenesis through their dynamic interactions with tumor-infiltrating immune cells, suggesting a crucial role in the tumor microenvironment.