First, we used differentially expressed LMGs, including CYP19A1, FABP4, LRP2, SLCO1A2, PPARGC1A and ALOXE3, to construct the LMrisk for predicting prognosis of colon cancer, and found that the LMrisk was associated with the immunosuppressive TME and predictive biomarkers of immunotherapeutic response in colon cancer. This evidence concerns the gene ALOXE3 and malignant colon neoplasm.