Identification and validation of a novel autophagy-related biomarker in obstructive sleep apnea syndrome.

STUDY

objectivesObstructive sleep apnea syndrome is closely associated with tumor growth. Chronic intermittent hypoxia promotes autophagy and is related to malignant tumor development. However, the role of autophagy in obstructive sleep apnea syndrome progression remains unclear.

methodsobstructive sleep apnea syndrome datasets (GSE135917 and GSE38792) from Gene Expression Omnibus were analyzed to identify differentially expressed genes and autophagy-related differentially expressed genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were conducted, and a protein-protein interaction network identified hub genes. Colorectal cancer datasets from The Cancer Genome Atlas were used for differential expression and survival analyses, along with gene set enrichment analysis and immune infiltration analysis. Chronic intermittent hypoxia-induced autophagy and oxidative stress were investigated in Sprague-Dawley rats using reactive oxygen species assays. Hub genes were validated in rats and obstructive sleep apnea syndrome patient samples.

resultsGene set enrichment analysis revealed significant differences in autophagy-related gene expression among obstructive sleep apnea syndrome patients. Hub genes ATG5, CASP1, MAPK8, EIF4G1, and TANK-binding kinase 1 were identified, with ATG5 and TANK-binding kinase 1 validated. Autophagy-related differentially expressed genes were predominantly upregulated in colorectal cancer tissues. TANK-binding kinase 1 expression in colorectal cancer patients was associated with enhanced sensitivity to immunotherapy and CD8 + T cell, macrophage, and regulatory T cell infiltration, potentially influencing the immune microenvironment. The animal experiments showed that chronic intermittent hypoxia increased reactive oxygen species levels, suggesting that chronic intermittent hypoxia plays a role in autophagy. TANK-binding kinase 1 expression was significantly higher in obstructive sleep apnea syndrome patients than in controls, and continuous positive airway pressure did not alter TANK-binding kinase 1 levels.

conclusionsThis study is the first to describe the potential contribution of TANK-binding kinase 1 to the development of obstructive sleep apnea syndrome and its potential as a novel biomarker and potential therapeutic target for obstructive sleep apnea syndrome.