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

Abstract

IntroductionChronic obstructive pulmonary disease (COPD) and lung cancer often coexist, but its pathophysiology and genomics features are still unclear.MethodsIn 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.ResultsA 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).ConclusionIn 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.