Key Genes Related to the Integrated Stress Response Identified Through Bioinformatics and Clinical Experiments in Ovarian Aging
Year: 2026
Type: article
Abstract: Background: Ovarian aging (OA) compromises female fertility, but its relationship with the integrated stress response (ISR) remains incompletely understood. This study aimed to identify ISR-related genes associated with OA and assess their expression through experimental validation. Methods: Differentially expressed genes from an OA-related transcriptomic dataset were intersected with ISR-related genes to identify candidates. Machine learning and receiver operating characteristic (ROC) curve analysis were used to prioritize key genes. Gene set enrichment analysis (GSEA) and immune cell enrichment analysis were performed to explore associated biological features. Gene expression was assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: BAG2, BLVRB, PHB2, and STC1 were identified as key genes, with individual areas under the ROC curve (AUCs) ranging from 0.73 to 0.77 in the discovery dataset. All four genes were downregulated in OA samples in the transcriptomic analysis. GSEA revealed enrichment of ribosome-related pathways in gene expression profiles correlated with BAG2, BLVRB, and PHB2 (adjusted P < 0.05). BLVRB expression was positively correlated with the estimated regulatory T-cell enrichment score (cor = 0.42, P = 0.013). RT-qPCR supported the downregulation of BAG2, BLVRB, and PHB2 in the OA group (P < 0.05), whereas the decrease in STC1 expression was not statistically significant (P = 0.0811). Conclusion: These findings identify four candidate ISR-related genes associated with OA, with experimental expression support for three genes. Their biological roles and clinical relevance require further investigation in independent cohorts and functional studies before diagnostic or therapeutic applications can be considered.
DOI: 10.2147/ijwh.s633360
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,836
OpenAlex ID: W7225176170