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ERAP2 as a Potential Marker for Ovarian Ageing and Spontaneous Ovulation Recovery in Women With Premature Ovarian
Tingting Meng1,2, Yunju Jo3, Shibo Wei3
1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China.
Objective:
To explore novel biomarkers for clinical prognosis in patients with ovarian ageing, especially in premature ovarian insufficiency (POI).
Design:
Prospective Cohort Study.
Setting:
Reproductive Hospital Affiliated with Shandong University, China.
Population:
Sixty POI patients and 60 control women recruited from 2018 to 2019.
Methods:
Machine learning algorithms were used to screen features of ovarian ageing from public ovarian transcriptome data. The candidate serum biomarker, endoplasmic reticulum aminopeptidase-2 (ERAP2), was compared between 60 POI patients and 60 control women. A prospective follow-up of 4 years was conducted on POI patients, and prediction models were established for intermittent recovery of ovarian function and clinical pregnancy based on serum ERAP2 levels.
Main Outcome Measures:
Intermittent recovery of ovarian function and clinical pregnancy.
Results:
Machine learning models identified ERAP2 as a novel biomarker associated with ovarian ageing. POI patients exhibited significantly elevated serum ERAP2 levels compared to controls (5.78 ± 2.29 ng/mL vs. 4.81 ± 2.20 ng/mL, p = 0.018). With a prospective follow-up of these POI patients, ERAP2 was found to be a new biomarker for predicting intermittent recovery of ovarian function (AUROC = 0.763, 95% CI 0.734-0.792) and clinical pregnancy (AUROC = 0.768, 95% CI 0.749-0.787). Integrating ERAP2 into existing indices significantly improved their prediction accuracy both in predicting intermittent recovery of ovarian function (IDI = 0.166, p = 0.008) and in clinical pregnancy (NRI = 0.442, p = 0.034; IDI = 0.208, p = 0.018).
Conclusions:
Serum ERAP2 can serve as a biomarker for intermittent recovery of ovarian function and clinical pregnancy in patients with POI. Combining ERAP2 with other clinical indicators may facilitate personalised intervention strategies for patients with POI in clinic.
