Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Plasma Micro-RNA Expression

Abstract

The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective “ENDO-miRNA” study were analyzed and all known human miRNAs were sequenced. For each miRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. miRNAs with an AUC ≥ 0.6 were selected for further analysis. A comprehensive review of recent articles from the PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases was performed to identify functions and pathways associated with the selected miRNAs. In total, 2633 miRNAs were found in the patients with endometriosis. Among the 57 miRNAs with an AUC ≥ 0.6: 20 had never been reported before; one (miR-124-3p) had previously been observed in endometriosis; and the remaining 36 had been reported in benign and malignant disorders. miR-124-3p is involved in ectopic endometrial cell proliferation and invasion and plays a role in the following pathways: mTOR, STAT3, PI3K/Akt, NF-κB, ERK, PLGF-ROS, FGF2-FGFR, MAPK, GSK3B/β–catenin. Most of the remaining 36 miRNAs are involved in carcinogenesis through cell proliferation, apoptosis, and invasion. The three main pathways involved are Wnt/β–catenin, PI3K/Akt, and NF–KB. Our results provide evidence of the relation between the miRNA profiles of patients with endometriosis and various signaling pathways implicated in its pathophysiology.

Liquid Biopsy in Endometriosis: A Systematic Review

“…In particular, liquid biopsy demonstrated that hsa-miR-29b-1-5p, hsa-miR-4748, hsa-miR-515-5p, hsa-miR-548j-5p, and hsa-miR-6502-5p were upregulated, whereas hsa-miR-3137 and hsa-miR-3168 were downregulated, with no specification of the relative expression pattern [ 99 ]. Both endometrial biopsies and plasma showed that miR-124-3p was downregulated in the Dabi et al analysis, even though the authors did not declare the stage of disease of the patients enrolled [ 100 ]. Regarding infertility, Xu et al enrolled 14 infertile endometriotic patients, with no specification of the stage of disease, in whose endometrial biopsies miR-1304-3p, miR-544b, miR-3684, miR-494-5p, miR-4683, and miR-6747-3p were upregulated, whereas miR-3935, miR-4427, miR-652-5p and miR-205-5p were downregulated [ 73 ].…”

“…On the other hand, there is little evidence about miRNA expression in endometriotic patients suffering from dysmenorrhea, but without infertility-related problems. Bendifallah et al showed upregulation of hsa-miR-29b-1-5p, hsa-miR-4748, hsa-miR-515-5p, hsa-miR-548j-5p and hsa-miR-6502-5p, whereas Dabi et al revealed upregulated miR-124-3p, even though neither of the studies specified the incidence of infertility in their cohorts [ 99 , 100 ]. Moreover, neither of the studies disclosed the difference in the relative expression of miRNAs between patients and controls [ 99 , 100 ].…”

“…Bendifallah et al showed upregulation of hsa-miR-29b-1-5p, hsa-miR-4748, hsa-miR-515-5p, hsa-miR-548j-5p and hsa-miR-6502-5p, whereas Dabi et al revealed upregulated miR-124-3p, even though neither of the studies specified the incidence of infertility in their cohorts [ 99 , 100 ]. Moreover, neither of the studies disclosed the difference in the relative expression of miRNAs between patients and controls [ 99 , 100 ]. Farsimadan et al isolated miRNAs in infertile endometriotic patients without any declared symptoms, and they highlighted the upregulation of miR-146a rs2910164 and miR-149 rs2292832, which showed an intermediate delta of relative expression between patients and controls, e.g., ≥2 > 4 Log2(ratio) [ 20 ].…”