Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease

Abstract

Purpose

Ferroptosis plays essential roles in the development of COPD. We aim to identify the potential ferroptosis-related genes of COPD through bioinformatics analysis.

Methods

The RNA expression profile dataset GSE148004 was obtained from the GEO database. The ferroptosis-related genes were obtained from the FerrDb database. The potential differentially expressed ferroptosis-related genes of COPD were screened by R software. Then, protein–protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed ferroptosis-related genes. Finally, hub gene-microRNA(miRNA), hug gene-transcription factor interaction networks were constructed by miRTarBase v8.0 and JASPAR respectively, and hub gene drugs were predicted by the Enrichr database.

Results

A total of 41 differentially expressed ferroptosis-related genes (22 up-regulated genes and 19 down-regulated genes) were identified between 7 COPD patients and 9 healthy controls. The PPI results demonstrated that these ferroptosis-related genes interacted with each other. The GO and KEGG enrichment analyses of differentially expressed ferroptosis-related genes indicated several enriched terms related to ferroptosis, central carbon metabolism in cancer, and the HIF-1 signaling pathway. The crucial miRNAs and drugs associated with the top genes were identified.

Conclusion

We identified 41 potential ferroptosis-related genes in COPD through bioinformatics analysis. HIF1A, PPARG, and KRAS may affect the development of COPD by regulating ferroptosis. These results may expand our understanding of COPD and might be useful in the treatment of COPD.

Keywords:

• ferroptosis
• COPD
• bioinformatics analysis
• gene expression omnibus dataset

Abbreviations

COPD, chronic obstructive pulmonary disease; GEO, gene expression omnibus dataset; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function; PPI, Protein–Protein Interaction; miRNAs, microRNAs; TFs, transcription factors; IL-6, Interleukin-6; IL-18, Interleukin-18; TNF-α, Tumor Necrosis Factor-alpha, DMT1: divalent metal transporter 1; FPN1, ferroportin 1; Dcytb, duodenal cyto-chrome b; TfR: Transferrin receptor.

Data Sharing Statement

The datasets analyzed in this paper can be found in the GEO database. A total of 369 ferroptosis-related genes were performed from the FerrDd Database

Ethics Approval

The study is approved by the Medical Ethics Committees, Zhongnan Hospital of Wuhan University (No.2020099K).

Acknowledgments

We thank Hong Duo (Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, Hubei, China) for the image technical support

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

Funding was not applicable.