Characteristics Of KRAS-Specific Mutations In Colorectal Cancer And Its Value In Evaluating Prognosis

Objectives: To study the characteristics of Kirsten rat sarcoma viral oncogene homolog(KRAS)specific mutations in colorectal cancer and to determine whether all KRAS mutations predict poor prognosis for in patients with colorectal cancer(CRC).Methods: Real-time PCR was used to detect the mutation of KRAS in 1164 cases of primary colorectal cancer(restriction of BRAF to wild type).Correlations between KRAS-mutation status and clinicopathological characteristics were retrospectively analyzed.The relationship between KRAS mutation status and clinical pathological factors was analyzed by ?2 test or Fisher exact probability method.The survival curve was calculated by Kaplan-Meier method and the survival time was calculated.Hazard ratios(HRs)and 95% confidence intervals(CIs)were estimated using Cox proportional hazard model.Results: KRAS mutations were identified in 490 patients(42.1%).The mutation rate for codon 12 was 72.7%,of which G12 D was the highest(47.5%)followed by G12V(30.6%).KRAS mutations were significantly more common in female CRC patients than that in male patients(44.5% vs 38.1%,P < 0.05).Compared with that of the left-sided colon,the right-sided colon presented with a significantly greater number of KRAS mutations(47.2% vs 35.5%,P < 0.05).The mutation rate of KRAS in CRC patients with elevated serum CA19-9 levels preoperatively was higher than that in normal patients(48.9% vs 36.7%,P < 0.05).Additionally,KRAS mutations were also more frequently observed in patients with preoperatively elevated serum CEA levels compared to that in normal patients(46.6% vs 35.0%,P < 0.05).The mutation rate of KRAS was different in diverse pathological types of CRC.Mucinous adenocarcinoma demonstrated the highest rate(52.9%)followed by tubular adenocarcinoma(40.3%)with other types of CRC having the lowest rate(22.2%).The differences among the groups was statistically significant(P < 0.05).The mutation rate for codon 13 was 22.0% of which all were G13 D.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.Mortality risk was significantly increased with G12 D 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).Conclusion: KRAS mutations occurred primarily in codons 12 and 13.Among seven common mutations,G12 D,G12V,and G13 D were the most common.Codon-12 mutations were predictive for a poor prognosis in Chinese patients with CRC.Specifically,G12 D and G12 V were independent prognostic factors for worse OS and PFS.Detection of KRAS-specific site mutations is helpful in assessing the prognosis of patients with colorectal cancer and guiding clinical individualized treatment.