• Hang Cao, Zelin Ma, Yuan Li, Yang Zhang, and Haiquan Chen.
• Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Shanghai Cancer Center, Fudan University, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
• J. Thorac. Cardiovasc. Surg. 2023 Dec 1; 166 (6): e479e499e479-e499.

ObjectivesThe role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma.MethodsData were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored.ResultsTwo hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively.ConclusionsThe KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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