Molecular gene mutation profiles, TMB and the impact of prognosis in Caucasians and east Asian patients with lung adenocarcinoma.

Abstract

BackgroundThe difference in molecular gene mutation profile, tumor mutational burden (TMB) and their prognostic effects in lung adenocarcinoma between different ethnic groups are still unknown. A retrospective analysis was used to investigate the differences in lung adenocarcinoma driver gene mutations, TMB, and their impact on prognosis across different ethnic groups.MethodsThe incidence of epidermal growth factor receptor (EGFR) mutations and follow-up data of 647 Chinese lung adenocarcinoma patients were compared with the data from 522 Caucasian patients in The Cancer Genome Atlas (TCGA) database. Moreover, a comprehensive analysis was performed to compare the differences in gene mutation frequency, signaling pathway variation, and TMB using the whole-exome sequencing (WES) data of Chinese patients with that of Caucasian patients.ResultsA comparison of tumor signaling pathways and gene mutation profiles between Caucasians and Chinese revealed ethnic variations in the incidence of mutations in TGF-β and RTK-RAS signaling pathways, with P values of 0.012 and 0.016, respectively. In the Caucasian population, the mutations in 5 signaling pathways and 18 genes were all significantly correlated with TMB, whereas in the Chinese population, only mutations in the Notch pathway and 6 genes were found to be associated with TMB-high. EGFR mutations showed a better prognosis in Chinese patients with lung adenocarcinoma, while the opposite was found in Caucasians patients.ConclusionsVariations in the incidence of mutations in signaling pathways involved in lung adenocarcinoma and the correlation of the signaling pathways with TMB may exist across different ethnic groups.