Salivary MicroRNA Signature for Diagnosis of Endometriosis

Sofiane Bendifallah; Stéphane Suisse; Anne Puchar; Léa Delbos; Mathieu Poilblanc; Philippe Descamps; Francois Golfier; Ludmila Jornea; Delphine Bouteiller; Cyril Touboul; Yohann Dabi; Emile Daraï

doi:10.3390/jcm11030612

Endometriosis · Diagnosis

Salivary MicroRNA Signature for Diagnosis of Endometriosis

Bendifallah S, Suisse S, Puchar A, Delbos L, Poilblanc M, Descamps P, Golfier F, Jornea L, Bouteiller D, Touboul C, Dabi Y, Daraï E

Published January 26, 2022 Journal of clinical medicine

DOI 10.3390/jcm11030612 PMID 35160066 PMC PMC8836532

RRM Academy Synopsis

Saliva microRNA signature separated endometriosis in 200 women

A saliva test of small RNA molecules, called microRNAs, separated women with endometriosis from women without it in internal testing. The study was prospective and included 200 women with chronic pelvic pain. The signature's best test split flagged 96.7% of women who had endometriosis.

Key Findings

The study enrolled 200 women with chronic pelvic pain suggestive of endometriosis: 153 (76.5%) had endometriosis and 47 (23.5%) did not (controls).
Sequencing of the 200 saliva samples mapped reads to 2561 known miRNAs, and Random Forest feature selection produced a signature of 109 miRNAs.
Across 10 randomly composed internal datasets, the most accurate split reached sensitivity 96.7%, specificity 100% and AUC 98.3%.
The lowest sensitivity across the 10 datasets was 80%.
Endometriosis was confirmed by surgery in 83 women (54.2%) and by MRI in 70 (45.8%). All 47 controls had surgery.

Interpretation

This prospective diagnostic-accuracy study collected saliva from January to June 2021. The 10 datasets were random draws from the same cohort, an internal cross validation, and the headline figures come from the most accurate one. The authors state that the signature needs external validation. The control group had 47 women, and 24 of them had no abnormality found. Some women in both groups had prior hormonal treatment that might have affected miRNA levels. The population included no adolescents, so the authors say the results cannot be extended to them.

RRM Context

Restorative reproductive medicine (RRM) starts with identifying the underlying condition. In this cohort, women with endometriosis waited a mean of 14.8 years (±17.88) from symptom onset to diagnosis. The authors propose that a validated saliva test could support earlier diagnosis. Excision is the surgical standard once endometriosis is found.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis.

Methods

We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm.

Results

Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%.

Conclusions

The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.

Topics

Endometriosis › Diagnosis › Biomarkers · General Gynecology › Pelvic Pain › Chronic Pelvic Pain · Diagnostics › Genetic and Immune Testing › Karyotype and Genetic Panels

Sofiane Bendifallah, Stéphane Suisse, Anne Puchar, Léa Delbos, Mathieu Poilblanc, Philippe Descamps, Francois Golfier, Ludmila Jornea, Delphine Bouteiller, Cyril Touboul, Yohann Dabi, Emile Daraï

S Bendifallah, S Suisse, A Puchar, L Delbos, M Poilblanc, P Descamps, F Golfier, L Jornea, D Bouteiller, C Touboul, Y Dabi, E Daraï

PMID 35160066 35160066 DOI 10.3390/jcm11030612 10.3390/jcm11030612 Bendifallah et al. 2022, Bendifallah 2022

Salivary MicroRNA Signature for Diagnosis of Endometriosis

Saliva microRNA signature separated endometriosis in 200 women

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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