Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Abstract

<i>KRAS</i> mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of <i>KRAS</i> mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between <i>KRAS</i> mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for <i>KRAS</i> mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, <i>KRAS</i> codon 12 mutations were more common in female patients (P<0.05). <i>KRAS</i> codon 13 mutations tended to arise in right-sided compared with left-sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with <i>KRAS</i> codon 12 wild-type, codon 12 mutations were markedly correlated with a poorer survival (log-rank P=0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1.069-5.004, P=0.03; HR=2.621, 95% CI=1.057-6.497, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples.