Circular RNA Expression of Peripheral Blood Mononuclear Cells Associated with Risk of Acute Exacerbation in Smoking Chronic Obstructive Pulmonary Disease

Abstract

Xu-Rui Shen,1,* Ying-Ying Liu,2,* Rui-Qi Qian,1,* Wei-Yun Zhang,2 Jian-An Huang,1 Xiu-Qin Zhang,1 Da-Xiong Zeng2 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiu-Qin Zhang, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel [phone], Email [email protected] Da-Xiong Zeng, Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, No. 9 Chongwen Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel [phone], Email [email protected]: Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening.Patients and Methods: We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The T-test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators.Results: Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P< 0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P< 0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P< 0.0001) as well as the year after (r=0.72, P< 0.0001). AUC: 0.79, 95% CI: 0.1210– 0.3209, P< 0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: − 0.1972--0.0739 (P < 0.0001).Conclusion: This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.Keywords: chronic obstructive pulmonary disease, circular RNAs, smoking, acute exacerbation, biomarker

Keywords

• chronic obstructive pulmonary disease
• circular rnas
• smoking
• acute exacerbation
• biomarker