Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury

Abstract

Background Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI. Methods Key genes associated with ferroptosis in ALI were identified by bioinformatics analysis. GSE104214, GSE18341, and GSE17355 datasets were downloaded from the Gene Expression Omnibus database. The signature genes were screened by least absolute shrinkage and selection operator (LASSO) regression, and the key genes of ALI were screened by weighted correlation network analysis (WGCNA), followed by immune infiltration analysis and functional enrichment analysis. In addition, mRNA expression of key genes in the lungs of mice with hemorrhagic shock and sepsis was verified. Results A total of 2132 differential genes were identified by various analyses, and nine characteristic genes were detected using Lasso regression. We intersected nine signature genes with WGCNA module genes and finally determined four key genes (PROK2, IL6, TNF, SLC7A11). All four key genes were closely correlated with immune cells and regulatory genes of ALI, and the expression of the four genes was significantly different in the lung tissues of hemorrhagic shock and sepsis models. Besides, the ferroptosis related molecules GPX4 and ACSL4 showed remarkable difference in these models. Conclusion These results indicate that PROK2, IL6, TNF, SLC7A11 may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.

Fatal COVID-19 pulmonary disease involves ferroptosis

“…A Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of published RNA-sequencing dataset revealed ferroptosisrelated differentially expressed genes and important biological processes including the oxidative stress response, MAPK, and PI3K-AKT signaling pathway associated with COVID-19 40 . A weighted gene co-expression network analysis (WGCNA) of RNA-sequencing dataset revealed four key genes, PROK2, IL6, TNF, SLC7A11, closely related to COVID-19 ALI 41 . Our analysis of RNA-sequencing dataset (GEO, GSE171524) is consistent with these previous reports, emphasizing the ferroptosis pathway, particularly the iron regulatory pathway associated with severe COVID-19 lungs.…”