Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis
Abstract Context Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been valida...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2019-06, Vol.104 (6), p.1999-2022 |
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| creator | Nisenblat, Victoria Sharkey, David J Wang, Zhao Evans, Susan F Healey, Martin Ohlsson Teague, E Maria C Print, Cristin G Robertson, Sarah A Hull, M Louise |
| description | Abstract
Context
Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts.
Objective
Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy.
Setting
Two university-based, public hospitals and a private gynecology practice in Australia.
Design and Participants
Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119).
Results
Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively.
Conclusion
Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups’ findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
The diagnostic accuracy of endometriosis-associated plasma miRNAs was tested in two large independent cohorts and none showed sufficient sensitivity and specificity for a noninvasive diagnostic. |
| doi_str_mv | 10.1210/jc.2018-01464 |
| format | Article |
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Context
Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts.
Objective
Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy.
Setting
Two university-based, public hospitals and a private gynecology practice in Australia.
Design and Participants
Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119).
Results
Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively.
Conclusion
Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups’ findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
The diagnostic accuracy of endometriosis-associated plasma miRNAs was tested in two large independent cohorts and none showed sufficient sensitivity and specificity for a noninvasive diagnostic.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2018-01464</identifier><identifier>PMID: 30608536</identifier><language>eng</language><publisher>Washington, DC: Endocrine Society</publisher><subject>Accuracy ; Adolescent ; Adult ; Australia ; Biomarkers ; Biomarkers - blood ; Case-Control Studies ; Circulating MicroRNA - blood ; Circulating MicroRNA - isolation & purification ; Diagnostic tests ; Endometriosis ; Endometriosis - blood ; Endometriosis - diagnosis ; Endometriosis - pathology ; Endometriosis - surgery ; Endometrium - diagnostic imaging ; Endometrium - pathology ; Female ; Gynecology ; Hospitals ; Humans ; Laparoscopic surgery ; Laparoscopy ; Menstrual cycle ; Menstrual Cycle - blood ; Menstrual Cycle - physiology ; MicroRNA ; Middle Aged ; miRNA ; Multiplex Polymerase Chain Reaction ; Predictive Value of Tests ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult</subject><ispartof>The journal of clinical endocrinology and metabolism, 2019-06, Vol.104 (6), p.1999-2022</ispartof><rights>Copyright © 2019 Endocrine Society 2019</rights><rights>Copyright © 2019 Endocrine Society.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>Copyright © 2019 Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-f5464dd564a4d0cf426503e93d70d2fadd65c7596272a165a7acda8ed9abc2403</citedby><cites>FETCH-LOGICAL-c460t-f5464dd564a4d0cf426503e93d70d2fadd65c7596272a165a7acda8ed9abc2403</cites><orcidid>0000-0001-8345-7812 ; 0000-0003-0347-604X ; 0000-0002-5669-4422 ; 0000-0002-4831-7950 ; 0000-0003-1813-3971</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2364239511?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,21367,27901,27902,33721,33722,43781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30608536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nisenblat, Victoria</creatorcontrib><creatorcontrib>Sharkey, David J</creatorcontrib><creatorcontrib>Wang, Zhao</creatorcontrib><creatorcontrib>Evans, Susan F</creatorcontrib><creatorcontrib>Healey, Martin</creatorcontrib><creatorcontrib>Ohlsson Teague, E Maria C</creatorcontrib><creatorcontrib>Print, Cristin G</creatorcontrib><creatorcontrib>Robertson, Sarah A</creatorcontrib><creatorcontrib>Hull, M Louise</creatorcontrib><title>Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Context
Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts.
Objective
Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy.
Setting
Two university-based, public hospitals and a private gynecology practice in Australia.
Design and Participants
Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119).
Results
Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively.
Conclusion
Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups’ findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
The diagnostic accuracy of endometriosis-associated plasma miRNAs was tested in two large independent cohorts and none showed sufficient sensitivity and specificity for a noninvasive diagnostic.</description><subject>Accuracy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Australia</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Circulating MicroRNA - blood</subject><subject>Circulating MicroRNA - isolation & purification</subject><subject>Diagnostic tests</subject><subject>Endometriosis</subject><subject>Endometriosis - blood</subject><subject>Endometriosis - diagnosis</subject><subject>Endometriosis - pathology</subject><subject>Endometriosis - surgery</subject><subject>Endometrium - diagnostic imaging</subject><subject>Endometrium - pathology</subject><subject>Female</subject><subject>Gynecology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Laparoscopic surgery</subject><subject>Laparoscopy</subject><subject>Menstrual cycle</subject><subject>Menstrual Cycle - blood</subject><subject>Menstrual Cycle - physiology</subject><subject>MicroRNA</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Multiplex Polymerase Chain Reaction</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>Young Adult</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kktr3DAUhUVo6EzSLrMthmy68eTqaXs5TCcPmCRDSKE7cSPJQYNtTSR7kX8fTyZNaGnRQqD7ncO5HBFyQmFGGYWzjZkxoGUOVChxQKa0EjIvaFV8IlMARvOqYL8m5CilDYyMkPwzmXBQUEqupuR63WBqMWv93c08ZT982jb4nK1863tns3XoXdd7bDLcDfGxC6n3JrsPoUlZHWK27GxoXR99SD59IYc1Nsl9fbuPyc_z5f3iMl_dXlwt5qvcCAV9Xssxq7VSCRQWTC2YksBdxW0BltVorZKmkJViBUOqJBZoLJbOVvhgmAB-TL7vfbcxPA0u9br1ybimwc6FIWlGlaDAGYgRPf0L3YQhdmM6zbgSjFeS0g_qERunfVeHPqLZmeq5KkupCgVypGb_oMZjXetN6Fztx_c_BPleYGJIKbpab6NvMT5rCnpXn94YvatPv9Y38t_ewg4PrbPv9O--PhYPw_Z_XvuvwF8AMJ-esg</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Nisenblat, Victoria</creator><creator>Sharkey, David J</creator><creator>Wang, Zhao</creator><creator>Evans, Susan F</creator><creator>Healey, Martin</creator><creator>Ohlsson Teague, E Maria C</creator><creator>Print, Cristin G</creator><creator>Robertson, Sarah A</creator><creator>Hull, M Louise</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8345-7812</orcidid><orcidid>https://orcid.org/0000-0003-0347-604X</orcidid><orcidid>https://orcid.org/0000-0002-5669-4422</orcidid><orcidid>https://orcid.org/0000-0002-4831-7950</orcidid><orcidid>https://orcid.org/0000-0003-1813-3971</orcidid></search><sort><creationdate>20190601</creationdate><title>Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis</title><author>Nisenblat, Victoria ; Sharkey, David J ; Wang, Zhao ; Evans, Susan F ; Healey, Martin ; Ohlsson Teague, E Maria C ; Print, Cristin G ; Robertson, Sarah A ; Hull, M Louise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-f5464dd564a4d0cf426503e93d70d2fadd65c7596272a165a7acda8ed9abc2403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Accuracy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Australia</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Circulating MicroRNA - blood</topic><topic>Circulating MicroRNA - isolation & purification</topic><topic>Diagnostic tests</topic><topic>Endometriosis</topic><topic>Endometriosis - blood</topic><topic>Endometriosis - diagnosis</topic><topic>Endometriosis - pathology</topic><topic>Endometriosis - surgery</topic><topic>Endometrium - diagnostic imaging</topic><topic>Endometrium - pathology</topic><topic>Female</topic><topic>Gynecology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Laparoscopic surgery</topic><topic>Laparoscopy</topic><topic>Menstrual cycle</topic><topic>Menstrual Cycle - blood</topic><topic>Menstrual Cycle - physiology</topic><topic>MicroRNA</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Multiplex Polymerase Chain Reaction</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nisenblat, Victoria</creatorcontrib><creatorcontrib>Sharkey, David J</creatorcontrib><creatorcontrib>Wang, Zhao</creatorcontrib><creatorcontrib>Evans, Susan F</creatorcontrib><creatorcontrib>Healey, Martin</creatorcontrib><creatorcontrib>Ohlsson Teague, E Maria C</creatorcontrib><creatorcontrib>Print, Cristin G</creatorcontrib><creatorcontrib>Robertson, Sarah A</creatorcontrib><creatorcontrib>Hull, M Louise</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nisenblat, Victoria</au><au>Sharkey, David J</au><au>Wang, Zhao</au><au>Evans, Susan F</au><au>Healey, Martin</au><au>Ohlsson Teague, E Maria C</au><au>Print, Cristin G</au><au>Robertson, Sarah A</au><au>Hull, M Louise</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>104</volume><issue>6</issue><spage>1999</spage><epage>2022</epage><pages>1999-2022</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Context
Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts.
Objective
Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy.
Setting
Two university-based, public hospitals and a private gynecology practice in Australia.
Design and Participants
Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119).
Results
Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively.
Conclusion
Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups’ findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
The diagnostic accuracy of endometriosis-associated plasma miRNAs was tested in two large independent cohorts and none showed sufficient sensitivity and specificity for a noninvasive diagnostic.</abstract><cop>Washington, DC</cop><pub>Endocrine Society</pub><pmid>30608536</pmid><doi>10.1210/jc.2018-01464</doi><tpages>24</tpages><orcidid>https://orcid.org/0000-0001-8345-7812</orcidid><orcidid>https://orcid.org/0000-0003-0347-604X</orcidid><orcidid>https://orcid.org/0000-0002-5669-4422</orcidid><orcidid>https://orcid.org/0000-0002-4831-7950</orcidid><orcidid>https://orcid.org/0000-0003-1813-3971</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2019-06, Vol.104 (6), p.1999-2022 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2164103204 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; ProQuest Central |
| subjects | Accuracy Adolescent Adult Australia Biomarkers Biomarkers - blood Case-Control Studies Circulating MicroRNA - blood Circulating MicroRNA - isolation & purification Diagnostic tests Endometriosis Endometriosis - blood Endometriosis - diagnosis Endometriosis - pathology Endometriosis - surgery Endometrium - diagnostic imaging Endometrium - pathology Female Gynecology Hospitals Humans Laparoscopic surgery Laparoscopy Menstrual cycle Menstrual Cycle - blood Menstrual Cycle - physiology MicroRNA Middle Aged miRNA Multiplex Polymerase Chain Reaction Predictive Value of Tests Prospective Studies Real-Time Polymerase Chain Reaction Reproducibility of Results Sensitivity and Specificity Young Adult |
| title | Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis |
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