Kenji Sawa1, Yasuhiro Koh2, Tomoya Kawaguchi3, Satoshi Kambayashi2, Kazuhisa Asai1, Shigeki Mitsuoka4, Tatsuo Kimura5, Naruo Yoshimura4, Naoki Yoshimoto4, Akihito Kubo6, Hideo Saka7, Akihide Matsumura8, Hideki Wanibuchi9, Nobuyuki Yamamoto2, Noritoshi Nishiyama10, Kazuto Hirata1. 1. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. 2. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 3. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. Electronic address: kawaguchi.tomoya@med.osaka-cu.ac.jp. 4. Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 5. Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. 6. Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan. 7. Department of Respiratory Medicine and Medical Oncology, Japanese National Hospital Organization, Nagoya Medical Center, Nagoya, Japan. 8. Department of Surgery, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Japan. 9. Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 10. Department of Thoracic Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Abstract
OBJECTIVES: Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) have been proposed to have a mutual developmental mechanism, but their association has not been fully understood. We aimed to examine the association of the mutational landscape of NSCLC with co-morbid COPD. MATERIALS AND METHODS: A total of 197 surgical specimens of early stage NSCLC were retrospectively collected from two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013. COPD and its severity were defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system. For molecular profiling of NSCLC patients with COPD, the extracted DNAs were deep-sequenced using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes. Logistic regression analysis was performed to evaluate the impact of COPD on the somatic mutations. RESULTS: The COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases. The non-COPD group (n=120) had 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology. The frequency of PIK3CA mutation was significantly higher in the COPD group than in the non-COPD group (10.4% vs. 1.7%, p=0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with no difference in the frequency between the two groups (17.2% vs. 17.0%). 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). CONCLUSIONS: PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology.
OBJECTIVES:Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) have been proposed to have a mutual developmental mechanism, but their association has not been fully understood. We aimed to examine the association of the mutational landscape of NSCLC with co-morbid COPD. MATERIALS AND METHODS: A total of 197 surgical specimens of early stage NSCLC were retrospectively collected from two independent sources, namely, the Japan Molecular Epidemiology for Lung Cancer Study and the Osaka City University Hospital cohort from 2010 to 2013. COPD and its severity were defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grading system. For molecular profiling of NSCLCpatients with COPD, the extracted DNAs were deep-sequenced using next generation sequence technologies for somatic mutations in a maximum 72 cancer-associated genes. Logistic regression analysis was performed to evaluate the impact of COPD on the somatic mutations. RESULTS: The COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3 patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma cases. The non-COPD group (n=120) had 53 SCC cases, 64 adenocarcinoma cases, and three cases with other histology. The frequency of PIK3CA mutation was significantly higher in the COPD group than in the non-COPD group (10.4% vs. 1.7%, p=0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with no difference in the frequency between the two groups (17.2% vs. 17.0%). 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). CONCLUSIONS:PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology.