摘要Background:Many studies have examined the role of genes,proteins,and microribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type Ⅰ(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95％confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Addi-tionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neu-trophil infiltration into CRC tissues by increasing neutrophil levels in the blood.