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BMC Cancer
Published in: BMC Cancer 1/2022

Open Access 01-12-2022 | Breast Cancer | Research

Meta-analysis of diagnostic cell-free circulating microRNAs for breast cancer detection

Authors: Emir Sehovic, Sara Urru, Giovanna Chiorino, Philipp Doebler

Published in: BMC Cancer | Issue 1/2022

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Abstract

Background

Breast cancer (BC) is the most frequently diagnosed cancer among women. Numerous studies explored cell-free circulating microRNAs as diagnostic biomarkers of BC. As inconsistent and rarely intersecting microRNA panels have been reported thus far, we aim to evaluate the overall diagnostic performance as well as the sources of heterogeneity between studies.

Methods

Based on the search of three online search engines performed up to March 21st 2022, 56 eligible publications that investigated diagnostic circulating microRNAs by utilizing Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) were obtained. Primary studies’ potential for bias was evaluated with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). A bivariate generalized linear mixed-effects model was applied to obtain pooled sensitivity and specificity. A novel methodology was utilized in which the sample and study models’ characteristics were analysed to determine the potential preference of studies for sensitivity or specificity.

Results

Pooled sensitivity and specificity of 0.85 [0.81—0.88] and 0.83 [0.79—0.87] were obtained, respectively. Subgroup analysis showed a significantly better performance of multiple (sensitivity: 0.90 [0.86—0.93]; specificity: 0.86 [0.80—0.90]) vs single (sensitivity: 0.82 [0.77—0.86], specificity: 0.83 [0.78—0.87]) microRNA panels and a comparable pooled diagnostic performance between studies using serum (sensitivity: 0.87 [0.81—0.91]; specificity: 0.83 [0.78—0.87]) and plasma (sensitivity: 0.83 [0.77—0.87]; specificity: 0.85 [0.78—0.91]) as specimen type. In addition, based on bivariate and univariate analyses, miRNA(s) based on endogenous normalizers tend to have a higher diagnostic performance than miRNA(s) based on exogenous ones. Moreover, a slight tendency of studies to prefer specificity over sensitivity was observed.

Conclusions

In this study the diagnostic ability of circulating microRNAs to diagnose BC was reaffirmed. Nonetheless, some subgroup analyses showed between-study heterogeneity. Finally, lack of standardization and of result reproducibility remain the biggest issues regarding the diagnostic application of circulating cell-free microRNAs.
Appendix
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Metadata
Title
Meta-analysis of diagnostic cell-free circulating microRNAs for breast cancer detection
Authors
Emir Sehovic
Sara Urru
Giovanna Chiorino
Philipp Doebler
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2022
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-022-09698-8

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