Chronic obstructive pulmonary disease (COPD) is a long-term lung disease characterized by irreversible lung damage resulting in airflow limitation, abnormal permanent air-space enlargement, and emphysema. Cigarette smoking is the major cause of COPD with 15% to 30% of smokers developing either disease. About 50% to 80% of patients with lung cancer have preexisting COPD and smokers who have COPD are at an increased risk for developing lung cancer. Therefore, COPD is considered an independent risk for lung cancer, even after adjusting for smoking. A crucial early event in carcinogenesis is the induction of the genomic instability through alterations in the mitotic spindle apparatus. To date, the underlying mechanism by which COPD contributes to lung cancer risk is unclear. We hypothesized that tobacco smoke carcinogens induce mitotic spindle apparatus abnormalities and alter expression of crucial genes leading to increased genomic instability and ultimately tumorigenesis. To test our hypothesis, we assessed the genotoxic effects of a potent tobacco-smoke carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)] on bronchial epithelial cells from patients with COPD and normal bronchial epithelial cells and identified genes associated with mitotic spindle defects and chromosome missegregation that also overlap with lung cancer. Our results indicate that exposure to NNK leads to a significantly altered spindle orientation, centrosome amplification, and chromosome misalignment in COPD cells as compared with normal epithelial cells. In addition, we identified several genes (such as AURKA, AURKB, and MAD2L2) that were upregulated and overlap with lung cancer suggesting a potential common pathway in the transition from COPD to lung cancer.

中文翻译：

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慢性阻塞性肺疾病细胞有丝分裂纺锤体异常：肺癌的潜在途径

慢性阻塞性肺疾病（COPD）是一种长期肺部疾病，其特征是不可逆的肺损伤，导致气流受限、异常的永久性气隙扩大和肺气肿。吸烟是慢性阻塞性肺病的主要原因，15% 至 30% 的吸烟者患有这两种疾病。大约 50% 至 80% 的肺癌患者既往患有慢性阻塞性肺病 (COPD)，患有慢性阻塞性肺病 (COPD) 的吸烟者患肺癌的风险增加。因此，即使在调整吸烟因素后，慢性阻塞性肺病也被认为是肺癌的独立风险。致癌过程中一个关键的早期事件是通过有丝分裂纺锤体的改变诱导基因组不稳定性。迄今为止，慢性阻塞性肺病导致肺癌风险的潜在机制尚不清楚。我们假设烟草烟雾致癌物诱导有丝分裂纺锤体异常并改变关键基因的表达，导致基因组不稳定性增加并最终导致肿瘤发生。为了检验我们的假设，我们评估了一种强效烟草烟雾致癌物 [4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮 (NNK)] 对 COPD 患者和正常人的支气管上皮细胞的基因毒性作用支气管上皮细胞，并鉴定出与有丝分裂纺锤体缺陷和染色体错误分离相关的基因，这些基因也与肺癌重叠。我们的结果表明，与正常上皮细胞相比，暴露于 NNK 会导致 COPD 细胞中纺锤体方向、中心体扩增和染色体错位显着改变。此外，我们还发现了几个基因（例如 AURKA、AURKB 和 MAD2L2）上调并与肺癌重叠，这表明从 COPD 转变为肺癌的潜在共同途径。