Comprehensive Molecular Profiling Reveals Unique Characteristics of Non-Small Cell Lung Cancer in Xuanwei, China

Abstract

Background: Xuanwei County in Southwest China shows the highest incidence and mortality rate of lung cancer compared to other regions in China. Although studies have reported distinct clinical characteristics of Xuanwei patients, the molecular features of non-small cell lung cancer (NSCLC) patients from Xuanwei remain unclear, we comprehensively characterized such cases using next-generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded tumour samples from 146 NSCLC patients of Xuanwei were collected for an NGS-targeted panel assay; their features were compared with those of normal Chinese and TCGA cohorts. Findings: Uncommon EGFR mutations were the predominant type of EGFR mutation in the Xuanwei cohort compared to that in the normal Chinese cohort (p<0·001). G719X (A/C/D/R/S) was the most common mutation site (47·6%), followed by S768I and L858R. A higher frequency of KRAS mutation and lower ALK rearrangement were observed in the Xuanwei cohort than in normal Chinese cohorts (p<0·01). Xuanwei patients showed a significantly higher tumour mutation burden (TMB) than the normal Chinese and TCGA cohorts (p<0·001). Furthermore, TMB of patients with uncommon EGFR mutations was significantly higher than that of those with common EGFR mutations (p<0·01). Our data indicated that NSCLC patients from Xuanwei harbouring G719X/S768I co-mutations may benefit from EGFR-TKI treatment. Interpretations: Comprehensive molecular profiling revealed unique genomic features of NSCLC patients from Xuanwei, highlighting the potential for improvements in targeted therapy and immunotherapy in these patients. Funding: The National Natural Science Foundation of China (81760554), Applied Basic Research in Yunnan Province (2017FE468-055), Kunming Medical Association Special Project for Applied Basic Research of Yunnan (2017FE467-142), Yunnan Province Health and Family Planning Commission Medical Reserve Talents Plan (H-201703). Declaration of Interest: ZJ, Z-SR, W-WJ, and Z-SY declare personal fees from OrigiMed, remaining authors have nothing to disclose. Ethical Approval: This study was approved by the Institution Review Board of the First Hospital of Kunming Medical University and conducted according to the Declaration of Helsinki. Informed consent was obtained from all enrolled patients.