Salivary MicroRNA Signature for Diagnosis of Endometriosis

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.

Plasma and Peritoneal Fluid ZEB Levels in Patients with Endometriosis and Infertility

“…Investigation of novel potential endometriosis biomarkers could lead to quicker identification of patients requiring treatment and shortening the diagnostic delay, which currently lasts up to several years [ 9 ]. As there are high potential benefits of having such markers, numerous studies analyzed the subject searching for a highly specific and sensitive diagnostic tool [ 40 , 41 ]. Unfortunately, in the results of our study, we did not observe any association between plasma or peritoneal fluid zinc finger E-box-binding homeobox 1 and 2 levels and the incidence of endometriosis.…”

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

“…As diseases are already or soon to be diagnosed earlier, minimally invasive VNS modalities should also be proposed as a first-line treatment in several indications [ 54 , 105 ]. Remarkably, transcutaneous auricular VNS was recently advocated for the treatment of endometriosis [ 106 ], which is especially interesting since the diagnosis of endometriosis has become available with a simple salivary test [ 107 ].…”

Hsa-mir-135a Shows Potential as A Putative Diagnostic Biomarker in Saliva and Plasma for Endometriosis

“…However, salivary miRNAs tend to be encased in exosomes, increasing their stability and attractiveness as biomarkers in this body fluid [ 37 , 38 , 39 ]. Currently, in the context of endometriosis, only one study has been published evaluating the differences in the levels of expression of salivary miRNAs and their putative application as a diagnostic biomarker for the disease [ 40 ]. The authors performed saliva miRNA sequencing and computed the saliva-based diagnostic signature for endometriosis based on a cohort of 200 patients and controls.…”