A1 Refereed original research article in a scientific journal
Molecular diagnosis of polycystic ovary syndrome in obese and non-obese women by targeted plasma miRNA profiling
Authors: Romero-Ruiz Antonio, Pineda Beatriz, Ovelleiro David, Perdices-Lopez Cecilia, Torres Encarnación, Vazquez Maria J, Guler Ipek, Jiménez Álvaro, Pineda Rafael, Persano Mariasara, Romero-Baldonado Christina, Arjona José E, Lorente Juan, Muñoz Concepción, Paz Elier, Garcia-Maceira Fe-Isabel, Arjona-Sánchez Álvaro, Tena-Sempere Manuel
Publisher: European society of endocrinology
Publication year: 2021
Journal: European Journal of Endocrinology
Journal name in source: European journal of endocrinology
Journal acronym: Eur J Endocrinol
Volume: 185
Issue: 5
First page : 637
Last page: 652
ISSN: 0804-4643
eISSN: 1479-683X
DOI: https://doi.org/10.1530/EJE-21-0552
Objective
Polycystic ovary syndrome (PCOS) is diagnosed based on the clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, such as obesity and insulin resistance. miRNA 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 quantitative real-timePCR 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 least absolute shrinkage and selection operator 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.
Capsule
We define a novel protocol, based on plasma miRNA profiling, for molecular diagnosis of PCOS. This tool not only allows proper discrimination of the condition in non-obese women but also permits distinction between PCOS and obesity, which often display overlapping clinical presentations.
