Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients

Abstract

The efficacy of epidermal growth factor-targeting therapies has been found to be limited in tumors with the wild-type K-RAS gene, suggesting a predictive value of K-RAS gene analysis in tumoral response. However, the prognostic value of K-RAS is controversial. This study included patients diagnosed with metastatic colorectal cancer. The presence of K-RAS mutations was analyzed, and the tumors positive for a K-RAS mutation were further analyzed to identify the mutation type. Similarly, the following clinical and pathological variables were also collected. The study was composed of 53.3 % of patients with wild-type K-RAS and 46.7 % of patients with mutated K-RAS (mutated codon 12 was the most frequent). With a mean follow-up of 15 months (range, 1-45), the median survival of patients with wild-type K-RAS was 31.6 months. The median survival was 24.8 months for patients with K-RAS mutated in codon 12 and 17.8 months for patients with mutated codon 13 (p = 0.37). In a univariate analysis, K-RAS was associated with stage IV at diagnosis (p < 0.005). When K-RAS was mutated, a lower overall survival was observed in cases of G → A transition compared with G → T transversion (19.5 vs. 24.2 months, respectively; p = 0.47). When the amino acid change resulted in an acidic substitution, survival was lower, but it increased when the substitution resulted in a polar or nonpolar amino acid (19.5 vs. 23.2 vs. 24.4 months, p = 0.79). The type of K-RAS mutation or amino acid changes may have prognostic implications in metastatic colon cancer patients. Further research is needed in patients treated in prospective controlled trials.