The Biological Processes of Ferroptosis Involved in Pathogenesis of COVID-19 and Core Ferroptoic Genes Related With the Occurrence and Severity of This Disease

Abstract

Background: A worldwide outbreak of coronavirus disease 2019 (COVID-19) has resulted in millions of deaths. Ferroptosis is a form of iron-dependent cell death which is characterized by accumulation of lipid peroxides on cellular membranes, and is related with many physiological and pathophysiological processes of diseases such as cancer, inflammation and infection. However, the role of ferroptosis in COVID-19 has few been studied. Material and Method: Based on the RNA-seq data of 100 COVID-19 cases and 26 Non-COVID-19 cases from GSE157103, we identified ferroptosis related differentially expressed genes (FRDEGs, adj. P-value < .05) using the “Deseq2” R package. By using the “clusterProfiler” R package, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Next, a protein-protein interaction (PPI) network of FRDEGs was constructed and top 30 hub genes were selected by cytoHubba in Cytoscape. Subsequently, we established a prediction model for COVID-19 by utilizing univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) regression. Based on core FRDEGs, COVID-19 patients were identified as two clusters using the “ConsenesusClusterPlus” R package. Finally, the miRNA-mRNA network was built by Targetscan online database and visualized by Cytoscape software. Results: A total of 119 FRDEGs were identified and the GO and KEGG enrichment analyses showed the most important biologic processes are oxidative stress response, MAPK and PI3K-AKT signaling pathway. The top 30 hub genes were selected, and finally, 7 core FRDEGs (JUN, MAPK8, VEGFA, CAV1, XBP1, HMOX1, and HSPB1) were found to be associated with the occurrence of COVID-19. Next, the two patterns of COVID-19 patients had constructed and the cluster A patients were likely to be more severe. Conclusion: Our study suggested that ferroptosis was involved in the pathogenesis of COVID-19 disease and the functions of core FRDEGs may become a new research aspect of this disease.

Fatal COVID-19 pulmonary disease involves ferroptosis

“…Single-nucleus transcriptomic profiling of COVID-19 lungs revealed important pathological hallmarks associated with SARS-CoV-2 infection including hyperinflammation, macrophage infiltration, alveolar epithelial cell exhaustion, parenchymal lung senescence, and fibrosis 27,39 . 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 .…”

Identification of cuproptosis-related molecular subtypes and a novel predictive model of COVID-19 based on machine learning

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