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

Abstract Study objectives Obstructive sleep apnea syndrome (OSAS) is closely associated with tumor growth. Chronic intermittent hypoxia (CIH) promotes autophagy and is related to malignant tumor development. However, the role of autophagy in OSAS progression remains unclear. Methods OSAS datasets (GSE135917 and GSE38792) from GEO were analyzed to identify differentially expressed genes (DEGs) and autophagy-related DEGs (a-DEGs). GO, KEGG, and GSEA were conducted, and a PPI network identified hub genes. CRC datasets from TCGA was used for differential expression and survival analyses, along with GSEA and immune infiltration analysis. CIH-induced autophagy and oxidative stress were investigated in Sprague-Dawley rats using ROS assays. Hub genes were validated in rats and OSAS patient samples. Results GSEA revealed significant differences in autophagy-related gene expression among OSAS patients. Hub genes ATG5, CASP1, MAPK8, EIF4G1, and TBK1 were identified, with ATG5 and TBK1 validated. A-DEGs were predominantly upregulated in CRC tissues. TBK1 expression in CRC 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 CIH increased ROS levels, suggesting that CIH plays a role in autophagy. TBK1 expression was significantly higher in OSAS patients than in controls, and continuous positive airway pressure (CPAP) did not alter TBK1 levels. Conclusions This study is the first to describe the potential contribution of TBK1 to the development of OSAS and its potential as a novel biomarker and potential therapeutic target for OSAS.