Mutations In KRAS Codon 12 Predict Poor Survival In Chinese Patients With Metastatic Colorectal Cancer

Background:KRAS mutations serve a function in tumorigenesis of colorectal cancer(CRC)and guide the use of targeted drugs.Nevertheless,evidence of the association between KRAS mutations and poor OS in patients with mCRC is obtained primarily in Western countries and certain Asian countries;few data about prognostic significance of KRAS mutations in mCRC are available in Chinese patients Objective:The current study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics,and their prognostic significance in Chinese patients with metastatic mCRC.Methods:Based on the database of Sir Run Run Shaw Hospital(Hangzhou,China),a total of 580 patients were searched with histologically confirmed CRC and imaging confirmed metastasis between January 2010 and June 2016,among which 135 patients were tested for mutations in KRAS gene and 128 in BRAF gene.All statistical analysis was performed with SPSS statistical softwareResults: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,KRAS codon 12 mutations were more common in female patients(P<0.05).KRAS codon 13 mutations tended to arise in right-sided colon cancer(P<0.05).Survival analysis was performed in 101 patients receiving primary tumor resection.Compared with KRAS 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].Conclusions: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.