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Meta-Analysis
. 2023 May 5;24(9):8270.
doi: 10.3390/ijms24098270.

MicroRNA Dysregulation in Early Breast Cancer Diagnosis: A Systematic Review and Meta-Analysis

Alejandro Garrido-Palacios  1 , Ana María Rojas Carvajal  1 , Ana María Núñez-Negrillo  1   2 , Jonathan Cortés-Martín  2   3 , Juan Carlos Sánchez-García  2   3 , María José Aguilar-Cordero  1   2
Affiliations
Meta-Analysis

MicroRNA Dysregulation in Early Breast Cancer Diagnosis: A Systematic Review and Meta-Analysis

Alejandro Garrido-Palacios et al. Int J Mol Sci. .

Abstract

Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents strong limitations in early ages where breast cancer is much more aggressive and fatal. MiRNAs present in numerous body fluids might represent a new line of research in breast cancer biomarkers, especially oncomiRNAs, known to play an important role in the suppression and development of neoplasms. The aim of this systematic review and meta-analysis was to evaluate dysregulated miRNA biomarkers and their diagnostic accuracy in breast cancer. Two independent researchers reviewed the included studies according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A protocol for this review was registered in PROSPERO with the registration number "CRD42021256338". Observational case-control-based studies analyzing concentrations of microRNAs which have been published within the last 10 years were selected, and the concentrations of miRNAs in women with breast cancer and healthy controls were analyzed. Random-effects meta-analyses of miR-155 were performed on the studies which provided enough data to calculate diagnostic odds ratios. We determined that 34 microRNAs were substantially dysregulated and could be considered biomarkers of breast cancer. Individually, miR-155 provided better diagnostic results than mammography on average. However, when several miRNAs are used to screen, forming a panel, sensitivity and specificity rates improve, and they can be associated with classic biomarkers such us CA-125 or CEA. Based on the results of our meta-analysis, miR-155 might be a promising diagnostic biomarker for this patient population.

Keywords: biomarkers; breast cancer; cancer; miRNA diagnostics; micro-RNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Adapted PRISMA flow diagram of trials.
Figure 2
Figure 2
QUADAS-2 diagram of studies selected for the meta-analysis.
Figure 3
Figure 3
Summary of studies [18,19,24,37,47,49] included in miR-155 meta-analysis.
Figure 4
Figure 4
Forest plot of the overall pooled sensitivity and specificity. Studies [18,19,24,37,47,49].
Figure 5
Figure 5
Forest plot of the overall pooled positive and negative likelihood ratios. Studies [18,19,24,37,47,49].
Figure 6
Figure 6
Fagan nomogram of microRNA-155 for diagnosis breast cancer.
Figure 7
Figure 7
Summary receiver operating curve (SROC) for breast cancer diagnosis.
Figure 8
Figure 8
Pooled results of the sample to investigate the potential origin of heterogeneity, presented in a Deeks’ funnel plot.
Figure 9
Figure 9
Subgroup analysis based on the source (serum) type of (a) sensitivity and specificity, (b) SROC curve, and (c) positive and negative likelihood ratios. Studies [18,19,24,37,47,49].
Figure 9
Figure 9
Subgroup analysis based on the source (serum) type of (a) sensitivity and specificity, (b) SROC curve, and (c) positive and negative likelihood ratios. Studies [18,19,24,37,47,49].
See this image and copyright information in PMC

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