Not all mutations of KRAS predict poor prognosis in patients with colorectal cancer.

ABSTRACT

The mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) has been reported to be prognostically important in patients with colorectal cancer (CRC). In this study, we investigated whether all KRAS mutations predict poor prognosis in patients with CRC. Our analysis of characteristics of KRAS 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 KRAS 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.