A Panel of Plasma miRNAs 199b-3p, 224-5p and Let-7d-3p as Non-Invasive Diagnostic Biomarkers for Endometriosis

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Plasma miR-199b-3p, miR-224-5p, and let-7d-3p levels, particularly in combination, show promise as non-invasive diagnostic biomarkers for endometriosis.

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This study assessed whether a plasma microRNA panel comprising miR-199b-3p, miR-224-5p, and let-7d-3p could diagnose endometriosis. Using peripheral blood from 25 women with laparoscopically confirmed endometriosis and 25 controls without evidence of endometriosis, the authors measured miRNA expression by RT-qPCR and evaluated diagnostic performance with ROC curves. The results showed miR-199b-3p upregulation (P<0.001) and miR-224-5p and let-7d-3p downregulation (P<0.001 and P<0.05, respectively), with individual AUCs of 0.843, 0.914, and 0.696 and a combined panel AUC of 0.992 (sensitivity 96%, specificity 100%). This paper does not explicitly discuss endometriosis limitations such as cohort size or validation approach beyond reporting diagnostic accuracy in this case-control sample, which is a caveat for generalizability. This paper is centrally about endometriosis — it tests a non-invasive plasma miRNA diagnostic panel for endometriosis.

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Abstract

The objective of this study was to investigate whether the combination of miR-224-5p, miR-199-3p, and let-7d-3p is a suitable diagnostic panel for endometriosis. Twenty-five women with endometriosis (case) and twenty-five women without any sign of endometriosis (controls) were included. Peripheral blood specimens were collected from all these women who were a proper candidate for laparoscopy before surgery. Total RNA was isolated to synthesize complementary DNA. Expression of miR-199b-3p, miR-224-5p, and let-7d-3p was analyzed by RT-qPCR. To estimate the performance of the identified miRNAs for endometriosis diagnosis, we performed ROC curves analysis. There was an upregulation of miRNAs 199b-3p (P value < 0.001) and down-regulation of 224-5p (P value < 0.001) and miRNA let-7d-3p (P value < 0.05) in women with endometriosis compared to non-endometriosis women. The diagnostic accuracy of miRNAs 199b-3p, 224-5p, and let-7d-3p was measured by AUC which was 0.843 (sensitivity = 96% and specificity = 80%), 0.914 (sensitivity = 84% and specificity = 80%), and 0.696 (sensitivity = 80% and specificity = 56%) for miRNAs 199b-3p, 224-5p, and let-7d-3p, respectively. In combination, they showed the highest accuracy with the AUC 0.992 (sensitivity = 96% and specificity = 100%). In conclusion(s) the levels of miRNAs 199b-3p, 224-5p, and Let-7d-3p in plasma are potential diagnostic biomarkers for endometriosis patients.
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Abstract

The objective of this study was to investigate whether the combination of miR-224-5p, miR-199-3p, and let-7d-3p is a suitable diagnostic panel for endometriosis. Twenty-five women with endometriosis (case) and twenty-five women without any sign of endometriosis (controls) were included. Peripheral blood specimens were collected from all these women who were a proper candidate for laparoscopy before surgery. Total RNA was isolated to synthesize complementary DNA. Expression of miR-199b-3p, miR-224-5p, and let-7d-3p was analyzed by RT-qPCR. To estimate the performance of the identified miRNAs for endometriosis diagnosis, we performed ROC curves analysis. There was an upregulation of miRNAs 199b-3p (P value < 0.001) and down-regulation of 224-5p (P value < 0.001) and miRNA let-7d-3p (P value < 0.05) in women with endometriosis compared to non-endometriosis women. The diagnostic accuracy of miRNAs 199b-3p, 224-5p, and let-7d-3p was measured by AUC which was 0.843 (sensitivity = 96% and specificity = 80%), 0.914 (sensitivity = 84% and specificity = 80%), and 0.696 (sensitivity = 80% and specificity = 56%) for miRNAs 199b-3p, 224-5p, and let-7d-3p, respectively. In combination, they showed the highest accuracy with the AUC 0.992 (sensitivity = 96% and specificity = 100%). In conclusion(s) the levels of miRNAs 199b-3p, 224-5p, and Let-7d-3p in plasma are potential diagnostic biomarkers for endometriosis patients. Similar content being viewed by others Data Availability All data and material of the current study are accessible and comply with field standards. Change history 01 February 2021 A Correction to this paper has been published: https://doi.org/10.1007/s43032-021-00470-0

References

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The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril. 1998;70(6):1101–8. Acknowledgments This study is part of the MSc thesis of the first author and was supported by Tehran University of Medical Sciences (Grant No: 36424) and is acknowledged by authors. Funding This study was financially supported by the Research Department of Tehran University of Medical Sciences (TUMS) (Grant No: 36424). Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of Interest The authors declare that that they have no conflict of interest in this study. Ethics Approval The questionnaire and methodology for this study was approved by the Human Research Ethics committee of the Tehran University of Medical science (Ethics approval number: IR.TUMS.MEDICINE.REC.1396.3898). Consent for Publication The authors consented to publish the results of this study. Code Availability Not applicable. Declarations Not applicable. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article was updated to correct an error in the title and in the sixth sentence of the abstract. Rights and permissions About this article Cite this article Zafari, N., Tarafdari, A.M., Izadi, P. et al. A Panel of Plasma miRNAs 199b-3p, 224-5p and Let-7d-3p as Non-Invasive Diagnostic Biomarkers for Endometriosis. Reprod. Sci. 28, 991–999 (2021). https://doi.org/10.1007/s43032-020-00415-z Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00415-z

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endometriosis

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Endometriosis MicroRNAs Adult Biomarkers Biomarkers Down-Regulation Endometriosis Endometriosis Female Gene Expression Profiling Humans MicroRNAs

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