SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease
Li Zhang, Xian Wen Sun, Yong Ding, Ya Ru Yan, Yi Wang, Chuan Xiang Li, Shi Qi Li, Liu Zhang, He Jie Song, Hong Peng Li, Qing Yun Li
Abstract
Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 ( SERPINA1 ) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β 1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1β levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1β levels. These findings may be of diagnostic value. Keywords: SERPINA1 methylation, lung squamous cell carcinoma, chronic obstructive pulmonary disease, male