Eur J Endocrinol. 2021 Aug 1:EJE-21-0552.R1. doi: 10.1530/EJE-21-0552. Online ahead of print.
ABSTRACT
OBJECTIVE: Polycystic ovary syndrome is diagnosed based on clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, as obesity and insulin-resistance. MicroRNAs have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical-tools.
METHODS: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean; non-PCOS/obese; PCOS/lean; and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800-human-miRNA panel, followed by targeted-qPCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs and build classification algorithms, considering PCOS and obesity as major categories.
RESULTS: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial LASSO-Regression and decision-tree models were built to reliably discriminate PCOS vs. non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers.
CONCLUSIONS: We define herein a robust method for molecular classification of PCOS, based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS, but also discrimination between PCOS and obesity.
PMID:34403358 | DOI:10.1530/EJE-21-0552
