Proteomics reveal serum biomarkers for early diagnosis in premature ovarian insufficiency
TL;DR
Five proteins, especially S100A8/S100A9, represent potential serum protein biomarkers for early POI diagnosis, and the combined signature of S100A8 and S100A9 yielded reliable discriminatory power and independent ELISA testing further validated their elevated serum levels and satisfactory diagnostic value for POI.
Abstract
Background Premature ovarian insufficiency (POI) leads to infertility with unclear mechanisms and scarce early diagnostic biomarkers. This study explored serum protein profiles to uncover POI molecular mechanisms and candidate biomarkers. Methods Label-free serum proteomics was performed using serum samples from 20 POI patients, 20 healthy controls (HC) and 20 menopausal women (MP) to screen differentially expressed proteins (DEPs). Bioinformatic analyses including functional enrichment and correlation analysis were carried out. Candidate markers were evaluated by ROC analysis and validated by ELISA in an independent cohort of 88 participants. Results Three groups had distinct proteomic profiles. We identified 54 DEPs between POI and HC, as well as 30 DEPs between POI and MP. Functional enrichment uncovered dysregulation in cytoskeleton organization and autoimmune response in POI. Five biomarkers (S100A8, S100A9, TUBA1A, TPM4, RAP1B) exhibited stable diagnostic performance across cohorts. The combined signature of S100A8 and S100A9 yielded reliable discriminatory power, and independent ELISA testing further validated their elevated serum levels and satisfactory diagnostic value for POI. Conclusions POI is characterized by abnormal cytoskeleton homeostasis and inflammatory dysregulation. Five proteins, especially S100A8/S100A9, represent potential serum protein biomarkers for early POI diagnosis.