KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma

作者：F.T. Gallina, Daniele Marinelli, Enrico Melis, D. Forcella, Riccardo Tajè, Simonetta Buglioni, Paolo Visca, Andrea Torchia, Fabiana Letizia Cecere, Andrea Botticelli, Daniele Santini, Gennaro Ciliberto, Federico Cappuzzo, Francesco Facciolo · 发表于：Lung Cancer · 年份：2023 · DOI：10.1016/j.lungcan.2023.107254 · 被引用次数：13 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、PI3K/AKT/mTOR signaling in cancer

KRAS G12C mutations are found in about 12–13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD 604 ) to further test the hypothesis in external cohorts. In the stage I IRE cohort we found a significant association between the KRAS-G12C mutation and worse DFS in multivariable analysis (HR: 2.47). In the TCGA-LUAD stage I cohort we did not find statistically significant associations between the KRAS-G12C mutation and DFS. In the MSK-LUAD 604 stage I cohort we found that KRAS-G12C mutated tumours had worse RFS when compared to KRAS-nonG12C mutated tumours in univariable analysis (HR 3.5). In the pooled stage I cohort we found that KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours (HR 2.6), to KRAS wild-type tumours (HR 1.6) and to any other tumours (HR 1.8); in multivariable analysis, the KRAS-G12C mutation was associated with worse DFS (HR 1.61). Our results suggest that patients with resected, stage I LUAD with a KRAS-G12C mutation may have inferior survival outcomes..