Integrative analysis of angiogenesis-related genes highlights prognostic indicators in colorectal cancer through single-cell sequencing and immune infiltration analysis

Angiogenesis plays a pivotal role in colorectal cancer (CRC) progression and is closely intertwined with the tumor microenvironment (TME) and immune infiltration. This study aimed to identify key angiogenesis-related genes (ARGs) with prognostic significance in colorectal cancer using integrative bioinformatics and single-cell transcriptomic analysis. 526 common differentially expressed genes (DEGs) were extracted from three Gene Expression Omnibus (GEO) datasets and intersected with ARGs from MSigDB, resulting in identification of 18 candidate genes. A protein-protein interaction (PPI) network was constructed using the STRING database, followed by the extraction of 10 hub genes using the Cytoscape software. Five hub genes (MMP14, CXCL12, SPP1, TIMP1, and VCAN) showed significant association with poor overall survival. Expression analysis using UALCAN revealed significant upregulation of these genes, and their correlation with tumor-stage-specific expression. Utilizing the Tumor Immune Estimation Resource (TIMER) database immune infiltration analysis was carried out to explore the immune landscape. Tumor Immune Single-cell Hub2 (TISCH2), Tumor Immunotherapy Gene Expression Resource (TIGER), IMMUcan scDB and single-cell TIME (scTIME) databases revealed the expression of these hub genes in key TME components including fibroblasts, macrophages, and endothelial cells, and their link to immunosuppressive landscapes. Additionally, we discovered a substantial positive correlation between the expression of these hub genes and immune infiltration cells, such as macrophages, myofibroblasts and regulatory T cells (Treg). Notably, CXCL12 and SPP1 were implicated in immune cell recruitment, while TIMP1 and MMP14 were associated with ECM remodeling and myeloid cell differentiation. This study highlights the relevance of ARGs in tumor progression, prognosis and immune infiltration in CRC, offering potential targets for novel therapeutic interventions.