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

Yanqing Xing; Liting Feng; Yangdou Dong; Yupeng Li; Lulu Zhang; Qiannan Wu; Rujie Huo; Yanting Dong; Xinrui Tian; Xinli Tian

doi:10.2147/JAA.S416276

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

J Asthma Allergy. 2023 Jul 12:16:689-710. doi: 10.2147/JAA.S416276. eCollection 2023.

Authors

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
² College of Basic Medicine, Shanxi Medical University, Taiyuan, People's Republic of China.
³ Department of Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China.

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: GSEA; GSVA; asthma; bioinformatics; ferroptosis; immune microenvironment.

Grants and funding

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