Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients

Frontiers in Oncology

Oncology

Min Zhou¹  Qiurui Zhang¹  Weiting Hu¹  Chengqiang Li²  Hecheng Li²  Xijia Feng²  Shengzhou Wang³  Debin Sun³  Zhao Peng³ 

[1] Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China;Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Genecast Biotechnology Co., Ltd., Wuxi, Jiangsu, China;

关键词: lung cancer;    chronic obstructive pulmonary disease;    genetic mutations;    PI3K-Akt signaling pathway;    tumor immune microenvironment;   

DOI  :  10.3389/fonc.2023.1169874

 received in 2023-02-21, accepted in 2023-05-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundChronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality worldwide. Studies have reported molecular alterations in patients with lung cancer and in patients with COPD. However, few investigation has been conducted on the molecular characteristics of lung cancer patients with COPD.Materials and methodsWe performed a retrospective cohort study that included 435 patients with pathologically confirmed lung cancer at the Ruijin Hospital. For patients with documented spirometry, Global Initiative for Chronic Obstructive Lung Disease criteria were used to define COPD. For patients without documented spirometry, chest computed tomography and other clinical information were used to define COPD. Tumor tissue DNA was extracted from formalin-fixed paraffin-embedded samples. DNA mutation analysis, multiplex immunohistochemistry (mIHC), calculation of tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and predication of neoantigens were performed.ResultsAlthough SNV mutations in lung cancer patients with COPD (G1 group) were generally higher than those in lung cancer patients without COPD (G2 group), the difference in the number of mutations was insignificant between the two groups. Of the 35 mutated genes, the number of them was higher in G1 than in G2, except that of EGFR. PI3K-Akt signaling pathway was enriched from significantly different genes. While TMB and MATH levels were not significantly different, the tumor neoantigen burdenwas markedly higher in G1 than that in G2. The level of CD68+ macrophages was significant higher in the stroma and total areas in the G1 group than in G2 group. The level of CD8+ lymphocytes was markedly higher in the stroma and showed a clear tendency forhigher expression in the G1 group than inthe G2 group. No significant differences were observed for the level of programmed death-ligand 1+ (PD-L1+), programmed death 1+ (PD-1+), and CD68PD-L1 in the stroma, tumor and total areas.ConclusionOur study revealed different genetic aberrations and pathways, higher neoantigen burden, and higher level of CD68+ macrophages and CD8+ T lymphocytes in lung cancer patients with COPD. Our investigation implies that the existence of COPD should be considered and immunotherapy is a potential choice when treating lung cancer patients with COPD.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Feng, Hu, Li, Sun, Peng, Wang, Li and Zhou