PIK3CA 突变作为伴有慢性阻塞性肺疾病的非小细胞肺癌的独特遗传特征：来自多机构队列的综合突变分析。
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.
机构信息
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
出版信息
Lung Cancer. 2017 Oct;112:96-101. doi: 10.1016/j.lungcan.2017.07.039. Epub 2017 Aug 7.
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.
目的
非小细胞肺癌（NSCLC）和慢性阻塞性肺疾病（COPD）被认为具有共同的发病机制，但它们的关联尚未完全阐明。本研究旨在探讨 NSCLC 突变谱与合并 COPD 的相关性。
材料和方法
本研究共回顾性收集了 2010 年至 2013 年来自两个独立来源的 197 例早期 NSCLC 手术标本，分别为日本肺癌分子流行病学研究和大阪城市大学医院队列。COPD 及其严重程度按照全球慢性阻塞性肺疾病倡议（GOLD）指南和分级系统进行定义。对于 COPD 患者的 NSCLC 分子谱分析，提取的 DNA 采用下一代测序技术进行最大 72 个癌症相关基因的体细胞突变深度测序。采用逻辑回归分析评估 COPD 对体细胞突变的影响。
结果
COPD 组（n=77）包括 56 例 GOLD 1 期和 21 例 GOLD 2 或 3 期患者，58 例鳞癌（SCC）和 19 例腺癌。非 COPD 组（n=120）有 53 例 SCC，64 例腺癌，3 例其他组织学类型。COPD 组 PIK3CA 突变的频率明显高于非 COPD 组（10.4%比 1.7%，p=0.015）。同时，NFE2L2 突变仅见于 SCC 病例，两组间无差异（17.2%比 17.0%）。在考虑 COPD 状态、年龄、吸烟剂量、病理分期和组织学的多变量逻辑回归模型中，COPD 状态下观察到更多的 PIK3CA 突变（比值比=5.31，95%可信区间：1.03-27.29，p=0.046）。
结论
PIK3CA 突变是 COPD 合并 NSCLC 的一个独特的遗传特征，与年龄、吸烟剂量、病理分期和组织学无关。
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