Abstract:

Objective To examine the clinicopathological characteristics and the prevalence of KRAS, NRAS, and BRAF mutations in colorectal cancer (CRC) patients stratified by microsatellite instability (MSI) status. Methods We performed a retrospective analysis of 204 consecutive CRC patients treated at Nanyang Central Hospital between April 2020 and April 2025. MSI status and KRAS, NRAS, and BRAF mutations were determined. Patients were classified as MSI-high (MSI-H; ≥2 unstable loci, n=31) or MSI-low/stable (MSI-L/MSS; <2 unstable loci, n=173). Clinicopathological variables and mutation frequencies were compared between groups. Multivariate logistic regression was used to identify independent predictors of MSI-H status. Associations between MSI status and gene mutations were assessed by Spearman correlation. Results Significant differences were observed between MSI-H and MSI-L/MSS groups in patient age, tumor differentiation, primary tumor site, and tumour node metastasis (TNM) stage (all P<0.05). NRAS mutation frequency did not differ between groups (P>0.05). MSI-H tumors showed a significantly lower frequency of KRAS mutations and a higher frequency of BRAF mutations compared with MSI-L/MSS tumors (P<0.05). In multivariate analysis, younger age, right-sided primary tumor location, TNM stage II, poor tumor differentiation, lower KRAS mutation frequency, and higher BRAF mutation frequency were independently associated with MSI-H status (P<0.05). Spearman correlation confirmed a negative correlation between KRAS mutation and MSI status and a positive correlation between BRAF mutation and MSI status (P<0.05). Conclusion MSI status in colorectal cancer is associated with distinct clinicopathological features and mutation profiles. MSI-H tumors are more likely in younger patients, to arise in the right colon, to present at stage II, and to be poorly differentiated; they are also characterized by lower KRAS mutation prevalence and higher BRAF mutation prevalence.

Key words: colorectal cancer, microsatellite instability state, pathological feature, gene mutation