Molecular and Clinicopathological Characteristics of Lung Cancer Concomitant Chronic Obstructive Pulmonary Disease (COPD)

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, but its pathophysiology and genomics features are still unclear. Methods: In this study, we retrospectively collected lung cancer concomitant COPD (COPD-LC) and non-COPD lung cancer (non-COPD-LC) patients, who performed next generation sequencing (NGS) and had clinicopathological information simultaneously. The COPD-LC data from the TCGA cohort were collected to conduct further analysis. Results: A total of 51 COPD-LC patients and 88 non-COPD-LC patients were included in the study. Clinicopathological analysis showed that proportion of male gender, older age, and smoking patients were all substantially higher in COPD-LC group than in non-COPD-LC group (all P<0.01). Comparing the genomic data of the two groups in our cohort, COPD-LC had higher mutation frequency of LRP1B (43% vs 9%, P = 0.001), EPHA5 (24% vs 1%, P = 0.002), PRKDC (14% vs 1%, P = 0.039), PREX2 (14% vs 0%, P = 0.012), and FAT1 (14% vs 0%, P = 0.012), which had a relationship with improved tumor immunity. Immunotherapy biomarker of PD-L1 positive expression (62.5% vs 52.0%, P = 0.397) and tumor mutation burden (TMB, median TMB: 7.09 vs 2.94, P = 0.004) also were higher in COPD-LC. In addition, RNA data from TCGA further indicated tumor immunity increased in COPD-LC. Whereas, COPD-LC had lower frequency of EGFR mutation (19% vs 50%, P = 0.013) and EGFR mutant COPD-LC treated with EGFR-TKI had worse progression-free survival (PFS) (HR = 3.52, 95% CI: 1.27–9.80, P = 0.01). Conclusion: In this retrospective study, we first explored molecular features of COPD-LC in a Chinese population. Although COPD-LC had lower EGFR mutant frequency and worse PFS with target treatment, high PD-L1 expression and TMB indicated these patients may benefit from immunotherapy.