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Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis.
J Clin Endocrinol Metab. 2019 06 01; 104(6):1999-2022.JC

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.

Authors+Show Affiliations

Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.School of Medicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Parkville, Victoria, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand. New Zealand Bioinformatics Institute, University of Auckland, Auckland, New Zealand.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. Department of Obstetrics and Gynaecology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

30608536

Citation

Nisenblat, Victoria, et al. "Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis." The Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 6, 2019, pp. 1999-2022.
Nisenblat V, Sharkey DJ, Wang Z, et al. Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis. J Clin Endocrinol Metab. 2019;104(6):1999-2022.
Nisenblat, V., Sharkey, D. J., Wang, Z., Evans, S. F., Healey, M., Ohlsson Teague, E. M. C., Print, C. G., Robertson, S. A., & Hull, M. L. (2019). Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis. The Journal of Clinical Endocrinology and Metabolism, 104(6), 1999-2022. https://doi.org/10.1210/jc.2018-01464
Nisenblat V, et al. Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis. J Clin Endocrinol Metab. 2019 06 1;104(6):1999-2022. PubMed PMID: 30608536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma miRNAs Display Limited Potential as Diagnostic Tools for Endometriosis. AU - Nisenblat,Victoria, AU - Sharkey,David J, AU - Wang,Zhao, AU - Evans,Susan F, AU - Healey,Martin, AU - Ohlsson Teague,E Maria C, AU - Print,Cristin G, AU - Robertson,Sarah A, AU - Hull,M Louise, PY - 2018/07/04/received PY - 2018/12/28/accepted PY - 2019/1/5/pubmed PY - 2020/5/6/medline PY - 2019/1/5/entrez SP - 1999 EP - 2022 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 104 IS - 6 N2 - 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/30608536/Plasma_miRNAs_Display_Limited_Potential_as_Diagnostic_Tools_for_Endometriosis_ DB - PRIME DP - Unbound Medicine ER -