In conclusion, the prognostic model based on the signature of the 12 genes (ADORA3, CPA3, CPM, EDN3, FCRL2, MFNG, NAT1, PCSK5, PPARGC1A, PRRX2, TNFRSF17, and WDR78) exhibited a relatively satisfactory and credible predictive power for the prognosis of colon cancer, making it a great potential biomarker. This evidence concerns the gene EDN3 and malignant colon neoplasm.