Accurate diagnosis of endometriosis using serum microRNAs
Accurate diagnosis of endometriosis using serum microRNAs
Accurate Diagnosis of Endometriosis Using Serum MicroRNAs.
Am J Obstet Gynecol. 2020 Mar 09;:
Authors: Moustafa S, Burn M, Mamillapalli R, Nematian S, Flores V, Taylor HS
BACKGROUND: Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a non-invasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms.
OBJECTIVE: To validate the use of a microRNA panel as a non-invasive diagnostic method for detecting endometriosis.
STUDY DESIGN: This was a prospective study evaluating subjects with a clinical indication for gynecologic surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p and let-7b were measured in serum by qRT-PCR in a blinded fashion, without knowledge of disease status. Receiver operating characteristic (ROC) analysis was performed on individual miRNAs, as well as combinations of miRNAs. An algorithm combining the expression values of these miRNAs, built using machine learning with a Random Forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent dataset of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance.
RESULTS: The mean age of women in the study population was 34.1 and 36.9 for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n=39). Subjects with endometriosis had significantly higher expression levels of four serum miRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum miRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual miRNAs had ROC areas under the curve (AUC) ranging from 0.68 to 0.92. A classifier combining these miRNAs yielded an AUC of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each miRNA based on rASRM staging revealed that all miRNAs could distinguish Stage I/II from control, and Stage III/IV from control, but that the difference between Stage I/II and Stage III/IV was not significant. Subgroup analysis revealed that neither phase of menstrual cycle or use of hormonal medication significantly impacted expression levels in the miRNAs used in our algorithm.
CONCLUSIONS: This is the first report showing that miRNA biomarkers can reliably differentiate between endometriosis and other gynecologic pathologies with an AUC > 0.9 across two independent studies. We validated the performance of an algorithm based on previously identified miRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis non-invasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated co-morbidities and healthcare costs.
PMID: 32165186 [PubMed – as supplied by publisher]
Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis.
Cell Biosci. 2020;10:12
Authors: Taghavipour M, Sadoughi F, Mirzaei H, Yousefi B, Moazzami B, Chaichian S, Mansournia MA, Asemi Z
MicroRNAs or miRNAs are a component of the non-coding RNAs family which is engaged in many cellular functions such as cell proliferation, apoptosis, gene expression, signaling pathways, angiogenesis, and etc. Endometriosis is a malignant gynecologic disorder occurring in women before menopausal age. Pathogenesis of this illness is still a discussion subject between the scientists but in our knowledge, microRNAs can be one of the possible involved factors. The purpose of this paper is to investigate the role of apoptotic activities of miRNAs in endometriosis. Accumulative evidence has demonstrated the role of cell proliferation, apoptosis, and invasion in the progression of these diseases. In this review, we looked into the specific role of apoptosis and its related genes and pathways in endometriosis and tied to present an explanation of how miRNAs can affect endometriosis by their apoptotic activities. What we found is that a great extent of miRNAs is involved in this illness and they are responsible for repressing apoptosis and progression of the disease. As a result, miRNAs have two different usages in endometriosis: biomarkers and potential therapeutic targets. In this review we gathered a great amount of evidence to inquire into the role of micro RNAs in inducing apoptosis and how this mechanism can be exerted for therapeutic purposes for endometriosis.
PMID: 32082539 [PubMed]
miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12.
Pflugers Arch. 2019 May 25;:
Authors: Zhang Y, Yan J, Pan X
Endometriosis is an estrogen-dependent disease that is characterized by pelvic pain and infertility. MicroRNAs have been shown to implicate in the progression of endometriosis. In our study, we used real-time PCR to evaluate the expression of miR-141-3p in endometrial samples. In addition, western blot analysis was used to assess the expression of Krüppel-like factor 12 (KLF-12). The proliferation and migration of ectopic endometrial stromal cells (ESCs) were determined by MTT assay and Transwell assay, respectively. Cell apoptosis was evaluated using a Cell Death Detection ELISA Plus kit. The results showed that miR-141-3p and KLF-12 were significantly different in paired ectopic and eutopic endometrial samples. miR-141-3p overexpression significantly restrained the proliferation and migration and promoted the apoptosis of ectopic ESCs, whereas a decreased level of miR-141-3p was associated with opposite results. Furthermore, dual-luciferase reporter assay confirmed that KLF-12 was a novel target of miR-141-3p, while it also decreased the effects of miR-141-3p on the proliferation, apoptosis, and migration of ectopic ESCs. Our data suggested that enhanced expression of miR-141-3p suppressed the proliferation and migration of ectopic ESCs and promoted their apoptosis via targeting KLF-12. Our results may provide a novel potential therapeutic target for the treatment of endometriosis.
PMID: 31129698 [PubMed – as supplied by publisher]