The co-mutation of EGFR and tumor-related genes leads to a worse prognosis and a higher level of tumor mutational burden in Chinese non-small cell lung cancer patients

Abstract

Background: Lung cancer is the leading cause of cancer mortality in China. The clinicopathologic features and genetic profile of Chinese lung cancer patients need to be investigated. This study evaluated the gene mutation profile, analyzed the frequency of concurrent genes in epidermal growth factor receptor (EGFR)mutant non-small cell lung cancer (NSCLC) patients, and determined its prognostic value. Methods: We collected the clinical data from 151 initially diagnosed patients NSCLC. Tumor samples underwent targeted next-generation sequencing (NGS). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: Among the 151 participants, the mutational profile revealed alterations in 29 genes, where TP53 (37.09%) and EGFR (30.46%) exhibited the highest mutation rates. Mutations in the EGFR gene were most prevalent (40%) in adenocarcinoma (LUAD) and were only present in 8.8% of participants with squamous cell carcinoma (LUSC). The most frequently mutated genes in LUAD patients were TP53 (47%), followed by KRAS (11.7%). In all 39 participants with EGFR mutations, TP53, KRAS, PIK3CA, APC, and FBXW7 were also mutated. Those with only EGFR mutation appeared to have a better prognosis; however, the difference was not statistically significant. Tumor mutational burden (TMB) was roughly significantly increased in patients who harbored EGFR and other mutant driver genes, compared with only EGFR mutant patients. The TMB value was significantly higher in those with P53 mutation than in P53 wild-type patients. Conclusions: We described the genetic profiles of NSCLC and compared the difference in genetic profiles between LUAD and LUSC. The concomitant genetic alterations might be a poor prognostic factor for patients with EGFR mutation, and TMB might be prognostically related to the co-mutations of EGFR and other genes.