Clinical characteristics and prognostic value of the KRAS G12C mutation in Chinese non-small cell lung cancer patients

作者：Si‐Yang Maggie Liu, Hao Sun, Jiaying Zhou, Guang‐Ling Jie, Zhi Xie, Yang Shao, Xian Zhang, Junyi Ye, Chunxiang Chen, Xu‐Chao Zhang, Qing Zhou, Jin‐Ji Yang, Yi-Long Lung Cancer Wu · 发表于：Biomarker Research · 年份：2020 · DOI：10.1186/s40364-020-00199-z · 被引用次数：71 · 研究领域：Lung Cancer Treatments and Mutations、Colorectal Cancer Treatments and Studies、Cancer therapeutics and mechanisms

Abstract Background The KRAS mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the KRAS G12C mutation in Chinese NSCLC patients are rarely reported. Methods Next-generation sequencing was used to confirm the KRAS mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort). Results In the mCohort, 3998 patients (9.8%) were confirmed to harbor a KRAS mutation, of whom 1179 (29.5%) had the G12C subtype. In the iCohort, 130 NSCLC patients (8.9%) had a KRAS mutation and 42 (32.3%) had the G12C subtype. The G12C subgroup included more male patients (85.2% vs 67.4%, P < 0.0001) and more smokers (76.2% vs 53.4%, P = 0.02) than did the non-G12C subgroup. Both the KRAS mutation group and KRAS G12C mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio [HR]KRAS = 1.50, P = 0.002; 18.3 vs 26.7 months, HRG12C = 1.66, P = 0.007). In Cox regression analysis, smoking (HR = 1.39, P = 0.05) and stage IV disease (HR = 2.72, P < 0.001) remained as independent predictors of shorter OS. Both the KRAS...