Not all mutations of <i>KRAS</i> predict poor prognosis in patients with colorectal cancer.

Abstract

The mutation of Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) has been reported to be prognostically important in patients with colorectal cancer (CRC). In this study, we investigated whether all <i>KRAS</i> mutations predict poor prognosis in patients with CRC. Our analysis of characteristics of <i>KRAS</i> mutations revealed the mutation rate for codon 12 was 72.7%, of which G12D was the highest (47.5%) followed by G12V (30.6%), and the mutation rate for codon 13 was 22.0%, of which all were G13D. In support of the concept that prognostic value of the <i>KRAS</i> codon-12 mutations is different from the codon-13 mutations, results from our Cox proportional hazard model studies showed that codon-12 mutations correlated with worse overall survival (OS; HR = 2.846, 95% CI: 1.967-4.118, P < 0.001) and progression free survival (PFS; HR = 2.011, 95% CI: 1.450-2.789, P < 0.001). No prognostic significance was revealed for codon-13 mutations. On further analysis, we found that mortality risk was significantly increased with G12D and G12V (G12D: HR = 2.802, 95% CI: 1.793-4.381, P < 0.001; G12V: HR = 2.802, 95% CI: 1.793-4.381, P < 0.001), as was the risk of disease progression (G12D: HR = 2.079, 95% CI: 1.396-3.099, P < 0.001; G12V: HR = 2.408, 95% CI: 1.517-3.822, P < 0.001). To conclude, our results support the concept that codon-12 mutations were predictive for a poor prognosis in Chinese patients with CRC. Specifically, G12D and G12V were independent prognostic factors for worse OS and PFS.