Abstract
BACKGROUND: Colorectal cancer (CRC) represents a crucial global public health concern, yet its molecular mechanisms underlying CRC are not completely comprehended. This study utilizes Mendelian randomization (MR) in conjunction with comprehensive transcriptome profiling to discover crucial genetic markers associated with CRC. METHOD: Using CRC datasets from The Cancer Genome Atlas (TCGA), R software analyzed differentially expressed (DEGs). eQTLs served as instrumental variables (IVs) to identify CRC genes by means of two-sample MR methods. Key CRC genes were found by intersecting DEGs with genome-wide association study (GWAS) data. The causal impacts of these intersecting genes were analyzed using Summary-data-based Mendelian Randomization (SMR). In order to validate the gene-disease associations, the GSE39582 dataset was employed, along with polymerase chain reaction (PCR) techniques. Subsequent studies defined the roles of these genes in the CRC pathophysiology, incorporating functional enrichment, Gene Set Enrichment Analysis (GSEA), TISCH, and immune cell infiltration analyses. RESULTS: MR, TCGA and SMR identified three key genes-MCM6, RAB6B, and CDC25B-that are closely linked to CRC. These genes play vital roles in activities like mitotic DNA replication and cell cycle regulation. Moreover, findings from CIBERSORT analysis showed a unique immune cell pattern in CRC, underscoring the importance of immune mechanisms in the development of this disease. MR results are confirmed by a cohort and polymerase chain reaction (PCR) assessments. CONCLUSION: Three critical CRC-affecting genes were identified, offering new molecular insights and potential research and treatment directions.