The prognostic value of Kirsten rat sarcoma viral oncogene homolog mutations in resected lung adenocarcinoma differs according to clinical features

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 163; no. 1; pp. e73 - e85
• Main Authors: Ma, Zelin, Zhang, Yang, Deng, Chaoqiang, Fu, Fangqiu, Deng, Lin, Li, Yuan, Chen, Haiquan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Adenocarcinoma of Lung - surgery; Biomarkers, Tumor - genetics; China - epidemiology; Female; Humans; KRAS mutation; lung adenocarcinoma; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Middle Aged; Mutation; Neoplasm Invasiveness - genetics; Neoplasm Staging - methods; part-solid nodule; Pneumonectomy - methods; Pneumonectomy - statistics & numerical data; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras) - genetics; Risk Assessment - methods; Sex Factors; Smoking - epidemiology; Survival Analysis; TNM stage I; China; CTR; KRAS mutation; NSCLC; OS; CI; lung adenocarcinoma; HR; prognosis; part-solid nodule; GGO; CT; TNM; TNM stage I; KRAS; IMA; WT; RFS
• ISSN: 0022-5223; 1097-685X; 1097-685X
• DOI: 10.1016/j.jtcvs.2020.05.097

The ninth edition of lung cancer staging system recommends that specific driver mutations should be considered as prognostic factors in survival models. This study comprehensively investigated the prognostic value of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with resected lung adenocarcinomas according to different clinicopathologic and radiologic characteristics. In total, 1464 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations from November 2008 to March 2015. Age, sex, smoking status, performance status, tumor–node–metastasis stage, radiologic features, and histologic subtypes were collected. Competing risk model was used to estimate the cumulative incidence rate of recurrence. Cox regression multivariable analyses on recurrence-free survival (RFS) and overall survival (OS) were performed. KRAS mutations were more frequent in male subjects (P < .001), current/former smokers (P < .001), invasive mucinous adenocarcinoma (P < .001), and solid tumors (P < .001). In general, KRAS-mutated patients had greater cumulative recurrence rate (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.23-3.08; P < .001) and worse overall survival (OS; HR, 1.88; 95% CI, 1.23-2.87; P < .001) than KRAS wild-type patients. The OS (P < .001) of patients harboring KRAS-G12C/V mutations was shorter than that of other KRAS-mutated patients. Cox multivariable analyses demonstrated that KRAS mutations were independently associated with worse RFS (HR, 5.34; 95% CI, 2.53-11.89; P = .001) and OS (HR, 2.63; 95% CI, 1.03-6.76; P = .044) in part-solid lung adenocarcinomas. For stage I patients, Cox multivariable analyses revealed that KRAS mutation was an independent risk factor for RFS (HR, 2.05; 95% CI, 1.19-3.56; P = .010) and OS (HR, 2.38; 95% CI, 1.29-4.40; P = .005). In this study, we revealed that KRAS mutations was an independent prognostic factor in part-solid tumors and in stage I lung adenocarcinomas. These findings may contribute to the ninth edition of lung cancer staging project. [Display omitted]