Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid

Abstract

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.

Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition

“…Among 466 differentially expressed miRNAs, miR-205-5p was selected using NGS and bioinformatic methods. Recently, Yang et al ( 2023) reported miR-205-5p expression in uterus fluid [34]. The cellular and molecular mechanisms underlying the association between miR-205-5p and endometrial receptivity were investigated using in vitro and in vivo models.…”

Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

“…miRNAs modulate processes such as cellular division, proliferation, differentiation, apoptosis, and blood vessel formation [ 76 ]. The modified expression of miRNAs has also been found in endometrial cancer, and it can influence angiogenesis processes by targeting genes involved in the functionality of endothelial cells, vascular permeability, and angiogenic signaling [ 77 , 78 ].…”

“…Several studies have investigated the potential of miRNAs as molecular biomarkers for prognosis in EC [ 112 ]. Overexpression of miR-21 and miR-183-5p have been associated with tumor aggressiveness, lymph node metastasis, and poorer prognosis in endometrial cancer [ 77 ]. Reduced expression of miR-205 has been associated with advanced-stage disease and poorer prognosis in endometrial cancer.…”