Characterization of Serum MicroRNAs Profile of PCOS and Identification of Novel Non-Invasive Biomarkers

Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS ha...

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Veröffentlicht in:Cellular physiology and biochemistry 2014-01, Vol.33 (5), p.1304-1315
Hauptverfasser: Long, Wei, Zhao, Chun, Ji, Chenbo, Ding, Hongjuan, Cui, Yugui, Guo, Xirong, Shen, Rong, Liu, Jiayin
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container_end_page 1315
container_issue 5
container_start_page 1304
container_title Cellular physiology and biochemistry
container_volume 33
creator Long, Wei
Zhao, Chun
Ji, Chenbo
Ding, Hongjuan
Cui, Yugui
Guo, Xirong
Shen, Rong
Liu, Jiayin
description Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.
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Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000358698</identifier><identifier>PMID: 24802714</identifier><language>eng</language><publisher>Basel, Switzerland: Cell Physiol Biochem Press GmbH &amp; Co KG</publisher><subject>Adult ; Apoptosis ; Biomarkers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Cell Cycle ; Computational Biology ; Female ; Gene Expression Profiling ; Humans ; Microarray ; MicroRNA ; MicroRNAs - blood ; MicroRNAs - genetics ; Original Paper ; PCOS ; Polycystic Ovary Syndrome - blood ; Polycystic Ovary Syndrome - diagnosis ; Polycystic Ovary Syndrome - genetics ; Polycystic Ovary Syndrome - pathology ; Young Adult</subject><ispartof>Cellular physiology and biochemistry, 2014-01, Vol.33 (5), p.1304-1315</ispartof><rights>2014 S. Karger AG, Basel</rights><rights>2014 S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-dc9c46b22ef75435a3ffedcc5c36589e337a89e65f7dd2e72976238c95d026073</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2102,27635,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24802714$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Long, Wei</creatorcontrib><creatorcontrib>Zhao, Chun</creatorcontrib><creatorcontrib>Ji, Chenbo</creatorcontrib><creatorcontrib>Ding, Hongjuan</creatorcontrib><creatorcontrib>Cui, Yugui</creatorcontrib><creatorcontrib>Guo, Xirong</creatorcontrib><creatorcontrib>Shen, Rong</creatorcontrib><creatorcontrib>Liu, Jiayin</creatorcontrib><title>Characterization of Serum MicroRNAs Profile of PCOS and Identification of Novel Non-Invasive Biomarkers</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. 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The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. 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subjects Adult
Apoptosis
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Cell Cycle
Computational Biology
Female
Gene Expression Profiling
Humans
Microarray
MicroRNA
MicroRNAs - blood
MicroRNAs - genetics
Original Paper
PCOS
Polycystic Ovary Syndrome - blood
Polycystic Ovary Syndrome - diagnosis
Polycystic Ovary Syndrome - genetics
Polycystic Ovary Syndrome - pathology
Young Adult
title Characterization of Serum MicroRNAs Profile of PCOS and Identification of Novel Non-Invasive Biomarkers
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