Abstract
e20060 Background: A mutual developmental mechanism has been proposed between NSCLC and COPD; however, the association is not fully understood. We previously reported that the mutations in PI3K/AKT/mTOR pathway and NFE2L2 were frequently observed and co-existed in NSCLC patients with COPD (Kawaguchi T, J Clin Oncol 34, 2016 [suppl; abstr 8526]). To further validate this finding, a new cohort was added and merged into the original cohort’s study. Methods: A total of 197 surgical specimens of early stage NSCLC including 90 newly added from Osaka City University hospital were collected between 2010 and 2013. Extracted DNAs were deep-sequenced using NGS technologies for somatic mutations in 72 cancer-associated genes for a molecular profiling in NSCLC patients with COPD. We defined COPD as presence of FEV1/FEV < 0.7 and classified the severity based on the Global Initiative for Chronic Obstructive Lung Disease. Results: The COPD group (N = 77) including 56 mild, 21 moderate/severe diseases, had 58 squamous cell carcinoma (SQ) and 19 adenocarcinoma (AD), with 70 smokers. The non-COPD group (N = 120) had 53 SQ, 64 AD and three others, with 78 smokers. The frequency of PIK3CA mutations was higher in COPD (10.4 %) than non-COPD (1.7 %), while in AD KRAS mutations were more frequent in COPD (21.1%) than non-COPD (9.4%). Notably, the frequency of PIK3CA mutations increased parallel to the COPD severity (p < 0.001). Meanwhile, NFE2L2 mutations were observed only in SQ, and no difference in the frequency was observed between the two groups (17.2% vs. 17.0%) unlike our previous analysis. In the multivariate logistic regression model, significantly more PIK3CA mutations were observed in the presence of COPD (Odds ratio = 5.47, 95%CI: 1.04-28.85, p = 0.045) with consideration of age, smoking dose, histology and pathological stage. The most frequent base substitution pattern in PIK3CA mutations was C > T change, suggesting the association with APOBEC-mediated mutagenesis. Conclusions: PIK3CA mutations are distinctive genetic features in NSCLC with COPD, regardless of age, smoking dose, histology and pathological stage.
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