PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer with chronic obstructive pulmonary disease: A comprehensive mutational analysis from a multi-institutional cohort

Kenji Sawa, Yasuhiro Koh, Tomoya Kawaguchi, Satoshi Kambayashi, Kazuhisa Asai, Shigeki Mitsuoka, Tatsuo Kimura, Naruo Yoshimura, Naoki Yoshimoto, Akihito Kubo, Hideo Saka, Akihide Matsumura, Hideki Wanibuchi, Nobuyuki Yamamoto, Noritoshi Nishiyama, Kazuto Hirata

研究成果: ジャーナルへの寄稿学術論文査読

21 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)96-101
ページ数6
ジャーナルLung Cancer
112
DOI
出版ステータス出版済み - 10-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 呼吸器内科
  • 癌研究

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