Key Genes Related to the Integrated Stress Response Identified Through Bioinformatics and Clinical Experiments in Ovarian Aging.
- 1Center of Reproductive Medicine, General Hospital of Southern Theater Command, Guangzhou, 510010, People's Republic of China.
Abstract
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. 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). 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). 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.
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BibTeX
@article{xian2026genes,
title = {{Key Genes Related to the Integrated Stress Response Identified Through Bioinformatics and Clinical Experiments in Ovarian Aging.}},
author = {Yexing Xian and Yan Huang and Xiaoyan Chen and Dewei Lin and Ying Ou and Xinyu Guo},
journal = {International journal of women's health},
year = {2026},
month = nov,
doi = {10.2147/ijwh.s633360},
url = {https://europepmc.org/article/MED/42999615},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Key Genes Related to the Integrated Stress Response Identified Through Bioinformatics and Clinical Experiments in Ovarian Aging.
AU - Yexing Xian
AU - Yan Huang
AU - Xiaoyan Chen
AU - Dewei Lin
AU - Ying Ou
AU - Xinyu Guo
PY - 2026
DA - 2026/11/03
JO - International journal of women's health
DO - 10.2147/ijwh.s633360
UR - https://europepmc.org/article/MED/42999615
AB - 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. 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). 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). 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.
SN - 1179-1411
ER -