Circulating miRNAs as Biomarkers for Endometriosis and Endometriosis-Related Ovarian Cancer-An Overview

Abstract

Early detection and accurate diagnosis are pivotal in the management of endometriosis and endometriosis-related ovarian neoplasms (ERONs), yet there is no clear common ground regarding their pathogenesis. Endometriosis is a debilitating pathology that profoundly impairs the quality of life. Although the spontaneous resolution of endometriosis is possible, studies suggest that it can be a progressive condition, and ERONs can develop. The gold standard for diagnosis remains as the invasive method of laparoscopy followed by histological confirmation. In recent years, novel biomarkers have been discovered. MicroRNAs (miRNA) represent important epigenetic modulators of gene expression and are very attractive as biomarkers due to their lower complexity, tissue specificity, and stability in bodily fluids. Several studies have advanced the possibility of miRNAs becoming potential biomarkers in endometriosis and ERONs. Our aim is to bring these studies together in order to have a better understanding of whether, how, and when miRNAs might be used as biomarkers for these pathologies.

Methods: We selected the reviewed papers from Google Academic, PubMed, and CrossRef. A total of eight studies met the inclusion criteria.

Results: MiR-200 family, miR-143, 145, miR-20a, and miR199a were the most commonly dysregulated miRNAs in endometriosis, and miR-200 family was found to be dysregulated in both ERONs and endometriosis.

Conclusions: No single miRNA was considered as a sole biomarker for this pathology. However, since the prognostic value of biomarkers is generally enhanced if more are assessed at the same time, a panel of miRNAs could be a better indicator of the disease.

Keywords: biomarker; endometriosis; endometriosis-related ovarian neoplasm; miRNA; reverse transcription polymerase chain reaction (RT-PCR).

Figure 1

The mechanism of the progression of endometriosis to endometriosis-related ovarian cancer (adapted after Tanase et al. [26] and Samartzis et al. [34]). The process is initiated by heme and iron-mediated oxidative stress, leading to chronic inflammation and repeated hemorrhage. The oxidative stress produces alterations at the DNA level. These free radicals species are generated by an integrated antioxidant defense mechanism, and their production is a prerequisite in modulating different biochemical functions [35]. During the malignant transformation of endometriosis, estrogen receptor (ER) down-regulation is observed. Loss of estrogen function, loss of heterozygosity (LOH), and the mutation of other specific genes represent the trigger factors for the switch from endometriosis to endometriosis-related ovarian neoplasms (ERONs). Additional genes, such as ARID1A, abnormalities, or other molecular alterations may lead to the progression towards ovarian cancer.