Our results showed that CREB3L1 expression was positively correlated with TMB and MSI in COAD and STAD, indicating that patients with COAD or STAD who express CREB3L1 highly may have better responses to immune checkpoint inhibitors, while a negative connection of CREB3L1 with TMB and MSI was detected in BRCA, CESC, HNSC, KIRC, and LUSC. The gene discussed is CREB3L1; the disease is colon adenocarcinoma.