Assessing differential microRNA expression in endometriotic implants

Abstract

Endometriosis is an estrogen-dependent disease that is characterized by the growth of endometrial tissue outside of the uterine cavity. The most common endometriotic lesions are ovarian endometrioma, peritoneal lesions, and deeply-infiltrating endometriosis. Ten percent of women in reproductive age are affected, a gross underestimate due to the delay in diagnosis and non-specific symptoms. The etiology of endometriosis is not well understood, making diagnosis difficult, and treatments suboptimal. Currently, laparoscopic surgery is the gold standard for diagnosis, however this method is invasive, costly, and physicians are often reluctant to send their patients to surgery without certainty of disease. It is therefore a research priority to identify a minimally-invasive biomarker for endometriosis. Over the years, the search for a biomarker has shifted from a single circulating biomarker, to a panel of circulating biomarkers, and finally to the advent of newer technologies. The studies of proteomics, genomics, phenomics, and metabolomics have shown some promise thus far. MicroRNAs, a discovery of genomics, are short, non-coding RNA strands that regulate mRNA expression by silencing or degrading the transcript. The dysregulation of miRNAs have been shown to contribute to the pathology of many gynecological conditions, and have shown to be dysregulated in endometriosis. To date however, results have been underwhelming due to differences in methodologies and failure to consider endometriosis as a heterogeneous disease. Three miRNAs were studied based on their prevalence in the literature (miR-9, -21, and -424), and three others (miR-10a, -10b, and -204) were measured based on their association with BDNF. In the current study, miR-204 expression was significantly lower (p=0.0016) in the eutopic endometrium of women with endometriosis compared to controls. Relative expression of miR-21, miR-424, and miR-10b differed significantly (p<0.05) across lesion types in women with exclusively endometriomas, peritoneal or deep-infiltrating lesions. Corresponding BDNF expression in the lesion types were inversely correlated to miRNA expression suggesting these miRNA regulate BDNF and are implicated in endometriosis pathology. Due to the findings that miRNAs are differentially expressed between endometriotic lesions, this study also suggests that, different lesion types are biochemically distinct.