Correlation analysis between RAS gene mutations and pathological morphological features in colorectal cancer

To examine associations between Kirsten rat sarcoma viral oncogene (KRAS) mutations and histopathological features in colorectal cancer and to evaluate their prognostic implications. A total of 256 patients with colorectal adenocarcinoma treated between January 2018 and December 2022 were retrospectively included. Rat sarcoma (RAS) gene mutations, covering 21 sites in KRAS and NRAS, were detected using the ADx-ARMS kit. Due to the low mutation rate of NRAS (3.9%) and its lack of significant correlation with pathological features (P > 0.05), further analysis focused on KRAS mutations. Tumor differentiation, mucinous components, and tumor budding were assessed by two pathologists in a double-blind manner. The relationship between KRAS mutation status and morphological features was analyzed using logistic regression, and the prognostic value was evaluated using the Cox proportional hazards model. The KRAS mutation rate was 52.7% (135/256), with the main subtypes being G12D (30.37%), G13D (20.00%), G12V (17.78%), and G12C (7.41%). Logistic regression showed that KRAS mutation independently predicted right-sided colon tumors (OR = 1.85, P = 0.017), high tumor budding (OR = 2.46, P = 0.002), and mucinous components (OR = 2.39, P = 0.012). It was also positively associated with PIK3CA co-mutation (OR = 2.15, P = 0.042). Overall survival (OS) was longer in patients with KRAS mutations than in those with wild-type KRAS (P = 0.013), was longer in KRAS-mutated than wild-type cases (P = 0.013), whereas progression-free survival (PFS) showed no significant difference. No survival differences were detected among KRAS subtypes. Multivariate Cox analysis showed that TNM stage IV (HR = 4.80), poor differentiation (HR = 2.00), and absence of primary tumor resection (HR = 3.20) were independent adverse prognostic factors. KRAS mutations are closely associated with aggressive pathological features in colorectal cancer, particularly tumor budding and mucinous differentiation. Histopathological evaluation may aid risk stratification alongside KRAS status. Prognostic assessment in clinical settings should take both TNM staging and KRAS status into account.