Differential expression of plasma­derived exosomal miRNAs in polycystic ovary syndrome as a circulating biomarker.

ABSTRACT

Identifying biomarkers with high sensitivity and stability is helpful for the timely and accurate diagnosis, and effective management of polycystic ovary syndrome (PCOS), a long-term, progressive endocrine disorder. Circulating microRNAs (miRNAs/miRs) are being increasingly recognized as promising biomarkers given the stability and enrichment of miRNAs in exosomes. The high sensitivity of the reverse transcription-quantitative PCR (RT-qPCR) has enabled accurate quantification of miRNAs and small fragments, present in a low abundance, in the circulation. In the present study, the potential of miRNAs in the diagnosis of PCOS was evaluated. Exosomal miRNAs were extracted and screened, and three miRNAs (miR-4488, miR-151a-5p, and miR-223-3p) were found to be differentially expressed between the PCOS group and age-matched controls by sequencing analysis. RT-qPCR was performed on a clinically confirmed PCOS cohort (n=107) and a non-PCOS control cohort (n=101) from South China to validate the PCOS-related RNA sequencing results. miR-151a-5p and miR-4488 expression levels were significantly upregulated, and miR-223-3p expression was downregulated in the PCOS cohort compared with the control cohort (P<0.05). The areas under the receiver operating characteristic curve were 0.889, 0.871, and 0.664 for miR-4488, miR-151a-5p, and miR-223-3p, respectively. Combining anti-Müllerian hormone levels with the three miRNAs resulted in an AUC of 0.967, and higher sensitivity and specificity. These results suggest that miRNAs may prove useful in the early diagnosis and effective management of PCOS, and that these three miRNAs may be involved in the pathogenesis of PCOS. In addition, bioinformatics analysis showed that these three exosomal miRNAs were involved in key signaling pathways related to cancer.