Sawa K, et al. – The association of the mutational landscape of non–small cell lung cancer (NSCLC) with co–morbid chronic obstructive pulmonary disease (COPD), was examined. It was observed that irrespective of age, smoking dose, pathological stage, and histology, PIK3CA mutation was a distinctive genetic feature of NSCLC with COPD.

Methods

• From two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013, a total of 197 surgical specimens of early stage NSCLC were retrospectively collected.
• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system defined COPD and its severity.
• The extracted DNAs were deep-sequenced, for molecular profiling of NSCLC patients with COPD, using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes.
• The impact of COPD on the somatic mutations was assessed by logistic regression analysis.

Results

• Data revealed 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases in the COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients.
• 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology were part of the non-COPD group (n=120).
• As compared to the non-COPD group (10.4% vs. 1.7%, p=0.015), the frequency of PIK3CA mutation was significantly higher in the COPD group.
• This study found NFE2L2 mutation only in SCC cases.
• There was no difference in the frequency between the two groups (17.2% vs. 17.0%).
• Moreover, in the multivariate logistic regression model with consideration for COPD status, age, smoking dose, pathological stage, and histology, significantly more PIK3CA mutation was observed in the presence of COPD (odds ratio=5.31, 95% CI: 1.03–27.29, p=0.046).