Mutational variants of KRAS gene versus Wild-type KRAS in the survival outcomes of Vietnamese colon cancer stage II-III

Background: Colon cancer is one of the most common cancers in Vietnam and globally. The KRAS gene (Kirsten rat sarcoma) is an oncogene showing a high mutation rate in colon cancer, affecting 30% to 40% of patients. The mutated KRAS gene, which keeps the MAPK signaling pathway permanently active, is considered a negative factor in the survival of colon cancer patients. Recently, several studies have been conducted to evaluate the specific prognoses related to distinct KRAS mutations, but the results were controversial. Mutations in different KRAS codons may impact colon cancer treatment models and prognoses. Therefore, the impacts of codon-specific KRAS mutations on survival require further clarification. This study aims to determine the associations between codon-specific KRAS mutations and survival in Vietnamese patients at stages II - III. Methods: A descriptive design was applied and included 158 colon cancer patients at stages II-III at Bach Mai Hospital from January 2016 to August 2020. Testing for KRAS mutations was performed with formalin-fixed, paraffin-embedded tissue, and KRAS mutations were detected with the KRAS XL StripAssay (ViennaLab, Austria). Results: Among 158 patients, 71 (44.9%) exhibited mutated KRAS genes. The most frequent mutated KRAS variant was p.Gly12Asp (G12D) at 35.2%; the proportion of KRAS G13D (p.Gly13Asp) was 15.5%. The 3-year DFS of the wild-type KRAS group was 60.3%, while that of the mutated KRAS Exon 2 group was 55.2%. The worse prognosis for DFS was observed in patients with KRAS codon 12 mutations (3-year DFS: 52.9%). Among them, patients with codon-specific KRAS mutations named p.Gly12Asp (G12D) and p.Gly12Val (G12V) experienced better prognoses (59.1% and 63.6%, respectively). However, the differences were not statistically significant (P > 0.05). Conclusion: KRAS p.Gly12Asp (G12D) was the most common type among mutated KRAS genes. Codon-specific KRAS mutation was not a prognostic factor for DFS and OS in colon cancer stages II-III. The results support the current clinical practice that determining specific codon KRAS gene status is not conventional testing for resected colon cancer stages II-III.