SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease

Li Yue Zhang; Xian Wen Sun; Yong Jie Ding; Ya Ru Yan; Yi Wang; Chuan Xiang Li; Shi Qi Li; Liu Zhang; He Jie Song; Hong Peng Li; Qing Yun Li

doi:10.2147/COPD.S368543

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease

Int J Chron Obstruct Pulmon Dis. 2022 Sep 6:17:2117-2125. doi: 10.2147/COPD.S368543. eCollection 2022.

Authors

Li Yue Zhang^#^{1

2}, Xian Wen Sun^#^{1

2}, Yong Jie Ding^#^{1

2}, Ya Ru Yan^{1

2}, Yi Wang^{1

2}, Chuan Xiang Li^{1

2

3}, Shi Qi Li^{1

2}, Liu Zhang^{1

2}, He Jie Song^{1

2}, Hong Peng Li^{1

2}, Qing Yun Li^{1

2}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
² Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
³ Department of Respiratory and Critical Care Medicine, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of Wuhan, Wuhan, People's Republic of China.

^# Contributed equally.

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)-β1 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; chronic obstructive pulmonary disease; lung squamous cell carcinoma; male.

MeSH terms

Biomarkers
DNA Methylation
Humans
Lung Neoplasms* / diagnosis
Lung Neoplasms* / genetics
Male
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / genetics
Serine Proteinase Inhibitors
alpha 1-Antitrypsin / genetics

Substances

Biomarkers
SERPINA1 protein, human
Serine Proteinase Inhibitors
alpha 1-Antitrypsin

Grants and funding

This study was supported by the National Key R&D Program of China (funding no. 2018YFC1311900), National Natural Science Foundation of China (founding no. 81570082, 81770084); Shanghai Municipal Key Clinical Specialty (shslczdzk02202); Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014); Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100); and Cultivation Project of Shanghai Major Infectious Disease Research Base (20dz2210500).