Comprehensive molecular characterizations of stage I-III lung adenocarcinoma with tumor spread through air spaces

• Published in: Frontiers in genetics Vol. 14; p. 1101443
• Main Authors: Ye, Ronghao, Yu, Yongfeng, Zhao, Ruiying, Han, Yuchen, Lu, Shun
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 02.02.2023
• Subjects: adenocarcinoma; disease-free survival (DFS); Genetics; lung cancer; next-generation sequencing (NGS); spread through air spaces (STAS); lung cancer; spread through air spaces (STAS); adenocarcinoma; disease-free survival (DFS); next-generation sequencing (NGS)
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2023.1101443

The aim of this study is to investigate integrative genomic spectra of stage I-III lung adenocarcinoma with tumor spread through air spaces (STAS). We retrospectively identified 442 surgically resected lung adenocarcinoma patients of pathological stage I-III in Shanghai Chest Hospital from January 2018 to February 2021. Surgically resected tissues were used for next-generation sequencing (NGS) with a panel of 68 lung cancer-related genes to profile comprehensive molecular characterizations. A total of 442 cases were analyzed, including 221 (50%) STAS-positive (SP) and 221 (50%) STAS-negative (SN) lung adenocarcinoma patients. In total, 440 cases (99.6%) were positive for the overall mutational spectrum, and the higher mutational genes were EGFR, TP53, KRAS, ALK, SMAD4, and ERBB2 (62%, 42%, 14%, 10%, 7%, and 7%, respectively). Compared with the SN population, there was significantly lower EGFR alteration in the single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, < 0.001) and significantly higher TP53 alteration in the SP population (49.8% vs 34.8%, = 0.002). EGFR L858R missense mutation (19.5% vs 37.6%, < 0.001) and ERBB2 exon 20 indel mutation (1.8% vs 5.9%, = 0.045) were more frequent in the SN population. The detection rate of ALK fusion rearrangements in the SP population was significantly higher than that in the SN population (13.1% vs 2.3%, < 0.001). In the analysis of signaling pathways, no significant difference was discovered between SP and SN patients. No difference in 1-year disease-free survival was observed between SP and SN patients in this study. Significant differences exist in stage I-III lung adenocarcinoma patients with STAS in molecular characterizations.