Different oncological features of colorectal cancer codon-specific mutations: Not codon 13 but codon 12 have prognostic value.

Background: Approximately 40% of colorectal cancer (CRC) cases are linked to Kirsten rat sarcoma viral oncogene homolog ( mutations. mutations are associated with poor CRC prognosis, especially codon 12 mutation, which is associated with metastasis and poorer survival. However, the clinicopathological characteristics and prognosis of codon 13 mutation in CRC remain unclear.

Aim: To evaluate the clinicopathological characteristics and prognostic value of codon-specific mutations, especially in codon 13.

Methods: This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019. Patients with mutation status confirmed by molecular pathology reports were included. The relationships between clinicopathological characteristics and individual codon-specific mutations were analyzed. Survival data were analyzed to identify codon-specific mutations as recurrence-related factors using the Cox proportional hazards regression model.

Results: Among the 2203 patients, the incidence of codons 12, 13, and 61 mutations was 27.7%, 9.1%, and 1.3%, respectively. Both codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics, but only codon 12 was associated with pathological features, such as stage of primary tumor (T stage), lymph node involvement (N stage), vascular invasion, perineural invasion, tumor size, and microsatellite instability. codon 13 mutation showed no associations (77.2% 85.3%, = 0.159), whereas codon 12 was associated with a lower 5-year recurrence-free survival rate (78.9% 75.5%, = 0.025). In multivariable analysis, along with T and N stages and vascular and perineural invasion, only codon 12 (hazard ratio: 1.399; 95% confidence interval: 1.034-1.894; = 0.030) among mutations was an independent risk factor for recurrence.

Conclusion: This study provides evidence that codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.