Exploration Of Ferroptosis-related Genes In Chronic Obstructive Pulmonary Disease And Their Function Based On Bioinformatics Analysis

BackgroundChronic Obstructive Pulmonary Disease(COPD)is a chronic airway disease characterized by airflow limitation that is not fully reversible.Ferroptosis is a new type of iron-dependent regulated cell death.In recent years,ferroptosis has caught more and more attention in the study of inflammatory and neoplastic diseases.The latest research suggests that ferroptosis plays an indispensable role in the occurrence and development of COPD,but the ferroptosis-related genes involved in COPD still need to be further explored.This study aimed to explore the potential ferroptosis-related genes of COPD based on Bioinformatics analysis and preliminarily verify them at the cellular experiment.MethodsThe gene chip data GSE38974 was obtained from the GEO database,and principal component analysis was performed on this dataset.Differential expression genes between the COPD group and the control group were obtained by the limma package in the R software.The ferroptosis-related genes were obtained from the FerrDb database.The intersection of differential expression genes and ferroptosis-related genes was further obtained as a differential expressed ferroptosis-related gene set of COPD.Then a protein-protein interaction(PPI)network was constructed,and GO analysis and KEGG analysis were performed.Finally,16HBE cells were induced with 5%cigarette smoke extract(CSE)to construct a vitro model,and real-time fluorescence quantification PCR(qRT-PCR)was used to detect messenger RNA(Messenger RNA,mRNA)expression levels of differential expressed ferroptosis-related gene set of COPD.ResultsThe results of principal component analysis indicated that the good degree of distinction of data in GSE38974.A total of 45 differential expressed ferroptosis-related gene set of COPD were obtained in this study,including 27 down-regulated and 18 up-regulated genes.The PPI network analysis indicated that genes have complex interactions at the protein level.In the results of GO analysis and KEGG analysis,we found that these genes are mainly related to ferroptosis,autophagy,immunity,oxidative stress,and the like.The preliminary validation of the vitro model showed that among the 20 genes initially validated,the mRNA levels of 3 genes were significantly down-regulated(P is 0.007 for EPAS1,P is 0.000 for CAV1,P is 0.002 for SCD)and the mRNA levels of 4 genes were significantly up-regulated(P is 0.000 for IL-6,P is 0.046 for HMOX1,P is 0.006 for GDF15,P is 0.048 for G6PD).The result is consistent with the ones of the bioinformatics analysis.ConclusionsWe found a total of 45 potential ferroptosis-related genes of COPD based on bioinformatics analysis.Among them,EPAS1,CAV1,SCD,IL-6,HMOX1,GDF15,and G6PD may play potential important roles in the occurrence and development of COPD,providing research of COPD new ideas.