Integrative bioinformatics analysis to identify novel biomarkers associated with non-obstructive azoospermia

Area of Science:

• Genetics
• Molecular Biology
• Reproductive Medicine

Background:

• Non-obstructive azoospermia is a significant cause of male infertility.
• The role of autophagy-related genes (ARGs) in azoospermia remains incompletely understood.
• Identifying specific ARGs can elucidate disease mechanisms and suggest therapeutic strategies.

Purpose of the Study:

• To identify ARGs associated with non-obstructive azoospermia.
• To explore the molecular mechanisms underlying azoospermia involving ARGs.
• To discover potential diagnostic biomarkers and therapeutic targets for azoospermia.

Main Methods:

• Downloaded azoospermia datasets from Gene Expression Omnibus.
• Obtained ARGs from the Human Autophagy-dedicated Database.
• Identified differentially expressed ARGs, constructed protein-protein interaction networks, and performed functional enrichment analyses.
• Analyzed immune cell infiltration and gene interactions (hub gene-miRNA-TF-RBP-drug network).

Main Results:

• Identified 46 differentially expressed ARGs enriched in autophagy pathways.
• Selected eight hub genes, with HSPA5 implicated in azoospermia.
• Found decreased activated dendritic cells in azoospermia patients.
• Observed strong correlations between hub genes (e.g., ATG3, KIAA0652, MAPK1, EGFR) and immune cell infiltration.

Conclusions:

• Eight hub genes, including EGFR, HSPA5, ATG3, KIAA0652, and MAPK1, show potential as diagnostic and therapeutic biomarkers for azoospermia.
• The study provides insights into potential molecular targets and mechanisms involved in azoospermia development.
• Further research into these ARGs could lead to novel treatment strategies for male infertility.