Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features.

OBJECTS: KRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathological characteristics and prognostic value of KRAS G12V mutation in LUAD.

METHODS: Data of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathological characteristics, postoperative outcomes and recurrence pattern were analyzed among groups.

RESULTS: In total, 3554 patients were wild-type, and 275 patients harbored KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). KRAS G12V mutation was more frequent in males, older patients (≥60), former/current smokers, radiologic solid nodules, and highly invasive histological subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison to WT tumors. KRAS G12V was more prevalent in older patients and had less lympho-vascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in KRAS G12V group. Multivariate analysis demonstrated that KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, while KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and loco-regional recurrence.

CONCLUSIONS: KRAS G12V mutation was associated with aggressive clinical-pathological phenotype and early recurrence. To note, this mutation exhibited significantly worse prognosis in part-solid and stage Ⅰ lung adenocarcinoma patients. Meanwhile, the prognostic significance of KRAS G12C and G12V variants were comparable.