Various impacts of driver mutations on the PD-L1 expression of NSCLC

We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included...

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Published in:	PloS one 2022-08, Vol.17 (8), p.e0273207-e0273207
Main Authors:	Chu, Cheng-Hsiang, Huang, Yen-Hsiang, Lee, Po-Hsin, Hsu, Kuo-Hsuan, Chen, Kun-Chieh, Su, Kang-Yi, Yu, Sung-Liang, Tseng, Jeng-Sen, Yang, Tsung-Ying, Chang, Gee-Chen
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma Anaplastic Lymphoma Kinase - genetics Apoptosis B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Biology and Life Sciences Biomarkers Cancer Cancer therapies Carcinoma, Non-Small-Cell Lung - pathology Cell death Chemotherapy Epidermal growth factor ErbB-2 protein Gene mutations Genetic aspects Health aspects Histology Humans Immunology Immunotherapy Kinases Lung cancer Lung cancer, Non-small cell Lung diseases Lung Neoplasms - pathology Medicine and Health Sciences Membrane proteins Metastasis Mutants Mutation Non-small cell lung carcinoma Oncology, Experimental Patients PD-L1 protein Physical Sciences Prognosis Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism Sarcoma Small cell lung carcinoma Tumors
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Summary:	We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10-4.88], P = 0.027 and 2.33 [95% CI 1.11-4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16-5.75], P = 0.020 and 2.44 [95% CI 1.11-5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72-4.34], P < 0.001 and 1.93 [95% CI 1.13-3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations.
ISSN:	1932-6203 1932-6203