%0 Journal Article %A Junchao Jiang %A Shengsong Chen %A Tao Yu %A Chenli Chang %A Jixiang Liu %A Xiaoxia Ren %A Hongtao Niu %A Ke Huang %A Baicun Li %A Chen Wang %A Ting Yang %T Dynamic analysis of gene signatures in the progression of chronic obstructive pulmonary disease %D 2022 %R 10.1183/23120541.00343-2022 %J ERJ Open Research %P 00343-2022 %X Purpose Oxidative stress is an important amplifying mechanism in chronic obstructive pulmonary disease (COPD), however, it is unclear how oxidative stress changes and its exact amplification mechanism in pathological process. We aimed to dynamically analyze the progression of COPD and further elucidate the characteristics of each developmental stage and unveil the underlying mechanisms.Methods We performed a holistic analysis by integrating GEO microarray datasets related to smoking, emphysema, and GOLD classification based on the concept of gene, environment and time (GET). Gene Ontology (GO), protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were used to explore the changing characteristics and potential mechanisms. Using lentivirus to promote HIF3A overexpression.Results In smokers versus nonsmokers, GO term mainly enriched in “negative regulation of apoptotic process”. In later transitions between stages, the main enriched terms were continuous progression of “oxidation-reduction process”, and “cellular response to hydrogen peroxide”. Logistic regression showed that these core DEGs had diagnostic accuracy in test (AUC=0.823) and validation (AUC=0.750) sets. GSEA and PPI network showed one of the core DEGs, HIF3A, strongly interacted with the ubiquitin-mediated proteolysis pathway. Overexpression of HIF3A restored SOD levels and alleviated the ROS accumulation caused by CSE treatment.Conclusion Oxidative stress was continuously intensified from mild emphysema to GOLD-4, thus, special attention should be paid to the identification of emphysema. Furthermore, the downregulated HIF3A may play an important role in the intensified oxidative stress in COPD.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Junchao Jiang has nothing to disclose.Conflict of interest: Shengsong Chen has nothing to disclose.Conflict of interest: Tao Yu has nothing to disclose.Conflict of interest: Chenli Chang has nothing to disclose.Conflict of interest: Jixiang Liu has nothing to disclose.Conflict of interest: Xiaoxia Ren has nothing to disclose.Conflict of interest: Hongtao Niu has nothing to disclose.Conflict of interest: Ke Huang has nothing to disclose.Conflict of interest: Baicun Li has nothing to disclose.Conflict of interest: Ting Yang has nothing to disclose.Conflict of interest: Chen Wang has nothing to disclose. %U https://openres.ersjournals.com/content/erjor/early/2022/10/27/23120541.00343-2022.full.pdf