SiHyun Cho1, Levent Mutlu2, Olga Grechukhina2, Hugh S Taylor3. 1. Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. 2. Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut. 3. Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut. Electronic address: hugh.taylor@yale.edu.
Abstract
OBJECTIVE: To evaluate whether microRNAs (miRNAs) associated with endometriosis are detectable in the circulation and could serve as potential noninvasive biomarkers for endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Twenty-four women with endometriosis and 24 women without the disease (controls). INTERVENTION(S): Serum samples collected from women undergoing laparoscopy for endometriosis and other benign gynecologic disease. MAIN OUTCOME MEASURE(S): Total RNA extracted from serum and quantitative reverse-transcription polymerase chain reaction to determine levels of miRNA let-7a-f and miR-135a,b. RESULT(S): The levels of circulating let-7b and miR-135a were statistically significantly decreased in women with endometriosis compared with controls, and let-7d and 7f showed a trend toward down-regulation. Let-7b expression strongly correlated with serum CA-125 levels and showed the highest area under the curve of 0.691. When the patients were analyzed according to phase of the menstrual cycle, the expression of let-7b, 7c, 7d, and 7e was statistically significantly lower in the women with endometriosis during the proliferative phase. Using a logistic regression model, we evaluated the diagnostic power of differently expressed miRNAs; the combination of let-7b, let-7d, and let-7f during the proliferative phase yielded the highest area under the curve value of 0.929 in discriminating endometriosis from controls. CONCLUSION(S): Several circulating miRNAs are differentially expressed in the sera of women with endometriosis compared with controls. The combination of serum let-7b, 7d, and 7f levels during the proliferative phase may serve as a diagnostic marker for endometriosis.
OBJECTIVE: To evaluate whether microRNAs (miRNAs) associated with endometriosis are detectable in the circulation and could serve as potential noninvasive biomarkers for endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Twenty-four women with endometriosis and 24 women without the disease (controls). INTERVENTION(S): Serum samples collected from women undergoing laparoscopy for endometriosis and other benign gynecologic disease. MAIN OUTCOME MEASURE(S): Total RNA extracted from serum and quantitative reverse-transcription polymerase chain reaction to determine levels of miRNA let-7a-f and miR-135a,b. RESULT(S): The levels of circulating let-7b and miR-135a were statistically significantly decreased in women with endometriosis compared with controls, and let-7d and 7f showed a trend toward down-regulation. Let-7b expression strongly correlated with serum CA-125 levels and showed the highest area under the curve of 0.691. When the patients were analyzed according to phase of the menstrual cycle, the expression of let-7b, 7c, 7d, and 7e was statistically significantly lower in the women with endometriosis during the proliferative phase. Using a logistic regression model, we evaluated the diagnostic power of differently expressed miRNAs; the combination of let-7b, let-7d, and let-7f during the proliferative phase yielded the highest area under the curve value of 0.929 in discriminating endometriosis from controls. CONCLUSION(S): Several circulating miRNAs are differentially expressed in the sera of women with endometriosis compared with controls. The combination of serum let-7b, 7d, and 7f levels during the proliferative phase may serve as a diagnostic marker for endometriosis.
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