Integrated Analysis of Human Microarray and Rat Transcriptome Identified New Gene Candidates for COPD Progression in Response to Cigarette Smoking

An integrated analysis of human microarray and rat transcriptomic data was performed to illustrate the pathologic effects of cigarette smoking (CS) on the gene expression profile and identify new gene candidates for chronic obstructive pulmonary disease (COPD) progression. Small airway epithelial samples of Human with different smoking status using fiberoptic bronchoscopy and corresponding rat lung tissues following 0, 3, and 6 months of CS exposure were obtained. Differential expression analysis was performed to identify differentially expressed genes (DEGs). Using qRT-PCR, the expression of the significant overlapping genes between human and rats were confirmed in 16HBE cells. 8 relevant studies comprising 293 individuals including phenotypically normal non-smokers, normal smokers, and COPD smokers were involved by searching the public databases. The integrated bioinformatic analysis of 8 human GEO datasets and rat transcriptome databases revealed 13 overlapping genes between humans and rats in response to CS exposure during COPD progression. Of these, 5 genes (AKR1C3, ERP27, AHRR, KCNMB2, and MRC1) were consistently identified in both the human and rat and validated by qRT-PCR. Among them, ERP27, KCNMB2, and MRC1 were newly identified candidate genes for COPD progression in response to CS. In addition, we also found that DEGs obtained from each expression profile dataset was better than combined analysis as more genes could be identified. The findings of the present study illustrated that integration of human microarray and rat transcriptome data might facilitate the discovery of new DEGs candidate of COPD progression in response to smoking. Funding Statement: This study was supported by grants from the National Key R&D Program of China (2016YFC0903700), National Natural Science Foundation of China (81520108001, 81770043 and 81700043), Guangzhou Department of Education (1201620007), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S155), the National Key R&D Program of China (2018YFC1311900), the Guangdong Natural Science Foundation (2020A1515010076), and the Research Projects of SKLRD (OP-201808, QN-201706, QN-201917, OP-201912). Declaration of Interests: The authors have no conflict of interest to declare. Ethics Approval Statement: The study was conducted according to the criteria set by the declaration of Helsinki, and written informed consent was obtained from all participants before data collection. The study was approved by the Institutional Review Board (GZMC 2009-08-1336).