Circulating MicroRNAs Identified in a Genome-Wide Serum MicroRNA Expression Analysis as Noninvasive Biomarkers for Endometriosis

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 1; pp. 281 - 289
• Main Authors: Wang, Wen-Tao, Zhao, Ya-Nan, Han, Bo-Wei, Hong, Shun-Jia, Chen, Yue-Qin
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.01.2013; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Biological and medical sciences; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Biomarkers - metabolism; Case-Control Studies; Endocrinopathies; Endometriosis; Endometriosis - blood; Endometriosis - diagnosis; Endometriosis - genetics; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genome-Wide Association Study; Genomic analysis; Humans; Medical sciences; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; Middle Aged; miRNA; Sensitivity and Specificity; Severity of Illness Index; Uterine Diseases - blood; Uterine Diseases - diagnosis; Uterine Diseases - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult; Obesity; Nutrition; Nutrition disorder; Biological marker; Endometriosis; Metabolic diseases; Identification; Gene expression; Female genital diseases; Non invasive method; Uterine diseases; Serum; Genome; Endocrinology; Nutritional status
• DOI: 10.1210/jc.2012-2415
• ISSN: 0021-972X; 1945-7197

Context:There is currently no reliable noninvasive biomarker for the clinical diagnosis of endometriosis. Previous analyses have reported that circulating microRNAs (miRNAs) can serve as biomarkers for a number of diseases.Objective:The study aims to detect the serum miRNAs that are differentially expressed between endometriosis patients and negative controls to evaluate the potential of these miRNAs as diagnostic markers for endometriosis.Design:A total of 765 serum miRNAs were profiled using a TaqMan microRNA array in a pool of 10 endometriosis patients and a pool of 10 negative controls, and a set of selected miRNAs were further analyzed in a validation cohort consisting of sera from 60 patients and 25 controls including 10 samples used in array profiling.Results:The relative expression levels of miR-199a and miR-122 were found to be up-regulated in endometriosis patient samples compared with control samples, whereas miR-145*, miR-141*, miR-542-3p, and miR-9* were down-regulated in endometriosis patients. Importantly, the relative expression of miR-199a (P < 0.05) and miR-122 can be used to discriminate between severe and mild endometriosis. We also found that miR-199a is well correlated with pelvic adhesion and lesion distribution (P < 0.05) and associated with hormone-mediated signaling pathways. Furthermore, we investigated the diagnostic value of these molecules and confirmed the optimal combination of miR-199a, miR-122, miR-145*, and miR-542-3p with area under the curve of 0.994 (95% confidence interval = 0.984–1.000, P < 0.001) and a cutoff point (0.4950) of 93.22% sensitivity and 96.00% specificity.Conclusions:Our study demonstrated that the circulating miRNAs miR-199a, miR-122, miR-145*, and miR-542-3p could potentially serve as noninvasive biomarkers for endometriosis. miR-199a may also play an important role in the progression of the disease. This is the first report that circulating miRNAs serve as biomarkers of endometriosis.