Exploration and Validation of Potential Biomarkers and Therapeutic Targets in Ferroptosis of Asthma

Abstract

Purpose

Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma.

Methods

Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay.

Results

We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls.

Conclusion

This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.

Keywords:

• asthma
• bioinformatics
• ferroptosis
• GSEA
• GSVA
• immune microenvironment

Abbreviations

FR-DEGs, Ferroptosis-related differentially expressed genes; DEGs, Differentially expressed genes; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSEA, Gene Set Enrichment Analysis; GSVA, Gene Set Variation Analysis; GEO, Gene Expression Omnibus; PCA, Principal component analysis; MF, Molecular function; CC, Cellular component; BP, Biological process; ROC, Receiver operating characteristic; HAECs, Human airway epithelial cells; ASM, Airway smooth muscle; PUFAs, Polyunsaturated fatty acids; ROS, Reactive oxygen species; GPx4, Glutathione peroxidase 4; RBP, RNA-binding protein; NETs, neutrophil extracellular traps; PEBP1, Phosphatidylethanolamine binding protein 1; TCR, T-cell receptor; DC, Dendritic cells.

Data Sharing Statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the second Hospital of Shanxi Medical University (approval number 2022 YX 079) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Acknowledgments

We gratefully acknowledge contributions from all authors and GEO databases.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This study was funded by key Research and Development Projects of Shanxi Province (201903D421066) and Basic Research Project of Shanxi Province (202203021211029).