Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD

Abstract

Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD. Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra. Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD. In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD. Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD. We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer.