High tumor mutation burden indicates better prognosis in colorectal cancer patients with KRAS mutations

OBJECTIVE: Colorectal cancer (CRC) is a common type of malignant tumor of the digestive tract. Tumor mutation burden (TMB) is a potential prognostic indicator of numerous malignant tumors. This study investigated the prognostic value of TMB in CRC. METHODS: This study analyzed the clinical and somatic mutation data of patients with CRC from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA) cohorts. The genetic landscape was visualized using the maftools package in R software. Survival curves were constructed using the Kaplan–Meier method, and Cox regression analysis was performed to confirm that TMB is an independent prognostic indicator. A nomogram was developed to construct the prognostic model, which was evaluated using the C-index, calibration curve, and decision curve analysis. RESULTS: In patients with CRC, APC mutations indicated longer overall survival (OS), whereas KRAS mutations indicated shorter OS. For all included patients, there was no significant difference in the OS between the TMB-high and TMB-low groups. For patients with KRAS mutations, the OS in the TMB-high group was longer than that in the TMB-low group. Cox regression analysis showed that TMB was an independent prognostic factor in CRC patients with KRAS mutations. This explains the good accuracy of the nomogram prognostic model using TMB and indicates its good prospect in clinical applications. CONCLUSIONS: A high TMB indicates better prognosis in CRC patients with KRAS mutations, thus confirming the value of TMB in clinical applications.