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. 2023 Dec 21:14:1320954.
doi: 10.3389/fneur.2023.1320954. eCollection 2023.

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Jing Huang #  1 , Hezi Zhang #  2 , Lichao Cao  2 , Fang Chen  2 , Weinan Lin  1 , Qinghua Lu  3 , Xiao Huang  3 , Qi Weng  2 , Qin Yang  3   4
Affiliations

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Jing Huang et al. Front Neurol. .

Abstract

Obstructive sleep apnea (OSA) is a common syndrome characterized by upper airway dysfunction during sleep. Continuous positive airway pressure (CPAP) is the most frequently utilized non-surgical treatment for OSA. Ferroptosis play a crucial role in the physiological diseases caused by chronic intermittent hypoxia, but its involvement in the development of OSA and the exact mechanisms have incompletely elucidated. GSE75097 microarray dataset was used to identify differentially expressed genes between OSA patients and CPAP-treated OSA patients. Subsequently, Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING database, and FerrDb database were conducted to analyze the biological functions of differentially expressed genes and screen ferroptosis-related genes. Finally, GSE135917 dataset employed for validation. There were 1,540 differentially expressed genes between OSA patients and CPAP-treated OSA patients. These differentially expressed genes were significantly enriched in the regulation of interleukin-1-mediated signaling pathway and ferroptosis-related signaling pathway. Subsequently, 13 ferroptosis-related genes (DRD5, TSC22D3, TFAP2A, STMN1, DDIT3, MYCN, ELAVL1, JUN, DUSP1, MIB1, PSAT1, LCE2C, and MIR27A) were identified from the interaction between differentially expressed genes and FerrDb database, which are regarded as the potential targets of CPAP-treated OSA. These ferroptosis-related genes were mainly involved in cell proliferation and apoptosis and MAPK signaling pathway. Furthermore, DRD5 and TFAP2A were downregulated in OSA patients, which showed good diagnostic properties for OSA, but these abnormal signatures are not reversed with short-term effective CPAP therapy. In summary, the identification of 13 ferroptosis-related genes as potential targets for the CPAP treatment of OSA provides valuable insights into the development of novel, reliable, and accurate therapeutic options.

Keywords: bioinformatics analysis; chronic intermittent hypoxia; continuous positive airway pressure; ferroptosis; obstructive sleep apnea.

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Conflict of interest statement

HZ, LC, FC, and QW were employed by Shenzhen Nuclear Gene Technology Co., Ltd. The remaining 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.

Figures

Figure 1
Figure 1
Flowchart of bioinformatics analysis.
Figure 2
Figure 2
Volcano plot of differentially expressed genes between OSA and CPAP-treated OSA in GSE75097.
Figure 3
Figure 3
Functional analysis of differentially expressed genes. (A) Differentially expressed genes-enriched GO categories. (B) KEGG pathways analysis of differentially expressed genes.
Figure 4
Figure 4
STRING database was used to construct PPI network.
Figure 5
Figure 5
Identification and functional enrichment analysis of ferroptosis-related genes. (A) Ferroptosis-related genes were obtained from the intersection of the FerrDb database with differentially expressed genes. (B) KEGG pathways analysis of ferroptosis-related genes using the Metascape website and DAVID database. (C) GO categories of ferroptosis-related genes using the Metascape website.
Figure 6
Figure 6
DRD5 and TFAP2A had the diagnostic value for OSA. (A) Volcano plot of differentially expressed genes between healthy samples and OSA in GSE135917. (B) Venn diagram showed the overlapping genes of 13 ferroptosis-related genes and differentially expressed genes of GSE135917. DEGs indicates differentially expressed genes and FRGs ferroptosis-related genes. (C) The diagnostic ROC curves of DRD5 and TFAP2A in OSA and healthy samples.
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