We found that three of the eight DEGs were negative prognostic factors consistently in two colon cancer cohorts, including COL5A2, EDNRA, and OLR1. The identification of transcriptional markers and miRNA–mRNA regulatory networks in CTS may provide insights into the mechanism of tumor immune microenvironment regulation in colon cancer. The gene discussed is EDNRA; the disease is malignant colon neoplasm.