The pathogenic mutations in smokers with non-small cell lung cancer: a next-generation sequencing study.

Background: Tyrosine kinase inhibitor (TKI)-targeted therapy has significantly improved the quality life of patients with advanced non-small cell lung cancer (NSCLC). Smoking is the main pathogenic factor of lung cancer. A number of the studies have analyzed smoking patients and nonsmoking patients as grouping factors, but few have examined the characteristic gene mutations in these groups. This study thus aimed to examine the characteristic pathogenic mutations in smokers with NSCLC. Methods: A total of 302 smokers with stage IIIB-IV NSCLC were recruited from Jilin Cancer Hospital between June 2022 and July 2024. Gene sequencing was performed on tumor tissues, pleural effusion cells, and plasma via next-generation sequencing (NGS). Results: A total of 302 smoking patients were enrolled in the study, with the median age of 65 years, among whom 77.48% (234/302) were males and 22.52% (68/302) were females. The sample types included tissue 237 samples, 55 plasma samples, and 10 pleural effusion samples. The mutation rates of common driving genes in smoking patients were as follows: EGFR, 34.8% (105/302); ALK, 3.3% (10/302); ROS1, 1.0% (3/302); KRAS, 15.9% (48/302); BRAF, 2.3% (7/302); MET, 2.3% (7/302); RET, 2.3% (7/302); and HER2, 1.0% (3/302). The mutation rate of EGFR in pleural effusion samples was higher than that in paraffin tissue and peripheral blood (driver gene mutations: χ2=6.906, P=0.03; EGFR: χ2=9.839, P=0.007; ROS1: χ2=8.854, P=0.01). The three highest frequencies of mutations were TP53 (134/201, 66.7%), LRP1B (41/201, 20.4%), and RB1 (28/201, 13.9%). Conclusions: EGFR and KRAS was the most common driver gene mutations and TP53 the most common concomitant mutation in advanced NSCLC patients with smoking. There were significant differences in gene mutations between the different sample types. Molecular typing via NGS can better guide targeted precise treatment.