Unraveling EGFR-TKI resistance in lung cancer with high PD-L1 or TMB in EGFR-sensitive mutations

Autor: Wuwu Ding, Pengmin Yang, Xiaokai Zhao, Xiaozhi Wang, Huaqing Liu, Qing Su, Xintao Wang, Jieyi Li, Ziying Gong, Daoyun Zhang, Xinwei Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Respiratory Research, Vol 25, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 1465-993X
DOI: 10.1186/s12931-023-02656-3
Popis: Abstract Background Although EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) have been extensively studied, certain patient subgroups remain with unclear mechanisms. This retrospective study analysed mutation data of NSCLC patients with EGFR-sensitive mutations and high programmed death-ligand 1 (PD-L1) expression or high TMB to identify primary resistance mechanisms. Methods Hybrid capture-based next-generation sequencing (NGS) was used to analyse mutations in 639 genes in tumor tissues and blood samples from 339 NSCLC patients. PD-L1 immunohistochemical staining was also performed on the same cell blocks. Molecular and pathway profiles were compared among patient subgroups. Results TMB was significantly higher in lung cancer patients with EGFR-sensitive mutations and high PD-L1 expression. Compared with the high-expression PD-L1 or high TMB and low-expression or TMB groups, the top 10 genes exhibited differences in both gene types and mutation rates. Pathway analysis revealed a significant mutations of the PI3K signaling pathway in the EGFR-sensitive mutation group with high PD-L1 expression (38% versus 12%, p
Databáze: Directory of Open Access Journals
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