Abstract
AIM: This study aimed to identify autophagy-related genes (ARGs) associated with non-obstructive azoospermia and explore the underlying molecular mechanisms. METHODS: Two datasets associated with azoospermia were downloaded from the Gene Expression Omnibus database, and ARGs were obtained from the Human Autophagy-dedicated Database. Autophagy-related differentially expressed genes were identified in the azoospermia and control groups. These genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction (PPI) network, and functional similarity analyses. After identifying the hub genes, immune infiltration and hub gene-RNA-binding protein (RBP)-transcription factor (TF)-miRNA-drug interactions were analyzed. RESULTS: A total 46 differentially expressed ARGs were identified between the azoospermia and control groups. These genes were enriched in autophagy-associated functions and pathways. Eight hub genes were selected from the PPI network. Functional similarity analysis revealed that HSPA5 may play a key role in azoospermia. Immune cell infiltration analysis revealed that activated dendritic cells were significantly decreased in the azoospermia group compared to those in the control groups. Hub genes, especially ATG3, KIAA0652, MAPK1, and EGFR were strongly correlated with immune cell infiltration. Finally, a hub gene-miRNA-TF-RBP-drug network was constructed. CONCLUSION: The eight hub genes, including EGFR, HSPA5, ATG3, KIAA0652, and MAPK1, may serve as biomarkers for the diagnosis and treatment of azoospermia. The study findings suggest potential targets and mechanisms for the occurrence and development of this disease.