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

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.