Authors

Hongfeng Wang1, 2, 3, #, shuiwang Hu4, #, Cuilian Zhang2, 3, Baoxia Gu2, 3, Yan Zhao2, 3, Qian Wang2, 3, Yingpu Sun1, *


Departments

1Reproductive Medicine Center, the First Affiliated Hospital of Zhengzhou University, No.1 East Jianshe Rd, Zhengzhou 450052, China - 2Reproductive Medicine Center, the People’s Hospital of Zhengzhou University, No.7 Weiwu Rd, Zhengzhou 450003, China - 3Reproductive Medicine Center, Henan Provincial People’s Hospital, No.7 Weiwu Rd, Zhengzhou 450003, China - 4Department of Pathophysiology, Southern Medical University, No.1023-1063 South Shatai Rd, Guangzhou 510515, China

Abstract

Purpose: To better understand the mechanisms underlying PCOS with hyperandrogenemia (PCOS-HA) and PCOS without hyperandrogenemia (PCOS-NHA) and to identify new potential biomarkers for accurate diagnosis. 

Methods: High-resolution label-free mass spectrometry was utilized first to study the differential proteome of plasma-derived exosomes from participants in a healthy Control study, PCOS-HA, and PCOS-NHA. And then the differentially expressed proteins (DEPs) were carried out by a series of bioinformatics analyses. Finally, two DEPs were verified by ELISA analysis. 

Results: Fifty-nine DEPs were identified between PCOS-HA and PCOS-NHA, among which 11 specific proteins were screened with Wayne’s analysis. The heatmap of cluster analysis indicated that the expression profiles of DEPs could be divided primarily into 10 clusters. Protein-protein interaction network analysis revealed that most of the DEPs may have direct or indirect interactions. GO clustering enrichment analysis showed that the DEPs were mainly enriched in the immune system according to biological processes, participated in catalytic activity regarding molecular functions, and located in an extracellular region from a cellular components perspective. KEGG pathways analysis indicated that DEPs were mainly enriched in PI3K-Akt cell-signaling pathway. Furthermore, the expressional levels of AGP1 and ZNF28 in plasma exosomes were validated by ELISA analyses, which were consistent with the proteomic results. 

Conclusions: This study has successfully screened DEPs of plasma exosomes between PCOS-HA and PCOS-NHA, and AGP1 and ZNF28 showed potential biomarkers for differential diagnosis of PCOS.

Keywords

Polycystic ovary syndrome, exosomes, plasma, hyperandrogenemia, proteomics.

DOI:

10.19193/0393-6384_2021_1_25