Circulating MicroRNAs as Promising Diagnostic Biomarkers for Patients With Glioma: A Meta-Analysis

Abstract

Backgrounds and Purpose: Currently, circulating microRNAs (miRNAs) are considered to be non-invasive diagnostic biomarkers in a broad range of tumors. Nevertheless, so far, miRNAs have not been fully applied to the clinic for routine screening in glioma patients. Thus, our goal is to evaluate the diagnostic performance of circulating miRNAs for gliomas via a meta-analysis. The present study is registered on the PROSPERO website, with the number CRD42020195883.Methods: Literature retrieval was implemented in the PubMed, Embase, and Web of Science databases using the established search strategy. We pooled the sensitivity, specificity, and its 95% confidence intervals (CIs) for the included studies using the Stata 14.0 software. In addition, the heterogeneity between studies was assessed via the Q statistics and I2 values calculated by a Chi-square test. A bivariate random effects model was selected due to significant heterogeneity. Specifically, for exploring the factors influencing the heterogeneity, we implemented subgroup and meta-regression analyses. Ultimately, a Deek's funnel plot asymmetry test was used to estimate the potential publication bias.Results: A total of 18 articles covering 24 studies were included, containing 2,170 glioma patients and 1,456 healthy participants. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.84 (95%CI: 0.79–0.87), 0.84 (95%CI: 0.80–0.88), 5.3 (95%CI: 4.1–6.8), 0.19 (95%CI: 0.15–0.25), 27 (95%CI: 18–41), and 0.91 (95%CI: 0.88–0.93), respectively. Additionally, the findings revealed that serum miRNAs and miRNA panels presented superior diagnostic performance.Conclusion: Thus, circulating miRNAs have the potential to serve as diagnostic biomarkers for gliomas, but need to be verified via a large pool of prospective studies. Additionally, specific miRNAs still need to be elucidated in the diagnosis of a glioma, especially in the early screening stage. The findings may provide diagnostic and therapeutic strategies for the glioma population.

The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas

“…We know that stable miRNA expression is measurable from bodily fluids such as cerebrospinal fluid or blood serum [ 20 , 21 ] but that specific miRNAs in the diagnosis of a glioma, in particular at the early stage, are still missing [ 22 ]. We thus next tested the possibility of directly assaying the microRNAs studied in this study from the patient’s blood sample.…”

“…Nevertheless, miRNAs have not yet come to be used in daily clinical practice. To relaunch the debate on their possible clinical interest, particularly for the diagnosis of patients with gliomas, a meta-analysis recently tested the diagnostic performance of circulating miRNAs for gliomas [ 22 ]. After analyzing 18 articles covering 24 studies containing 2170 glioma patients and 1456 healthy participants, the authors concluded that circulating miRNAs have the potential to serve as diagnostic biomarkers for gliomas.…”

“…This result raises the question of what methodological choices should be made when one wants to use miRNAs as diagnostic and/or monitoring tools for patients with tumors and more particularly gliomas. Although circulating miRNAs are promising diagnostic biomarkers for patients with glioma, the serum miRNAs and miRNA panels presented a superior diagnostic performance compared to the use of only one miRNA [ 22 ]. Moreover, variations in the plasma concentrations of only one miRNA could alternatively reflect another cancer pathology in the same patient and not be specific to glioma, thus compromising the potential clinical utility in diagnosis and follow-up by leading to false detection.…”

“…Interestingly, the detection of stable miRNA expression in cerebrospinal fluid, blood serum, and other bodily fluids has led to the possibility of using miRNAs as non-invasive biomarkers for clinical applications [ 20 , 21 ]. However, specific miRNAs still need to be elucidated in the diagnosis of a glioma, especially in the early screening stage [ 22 ].…”

Complementary Nuclear Magnetic Resonance-Based Metabolomics Approaches for Glioma Biomarker Identification in a Drosophila melanogaster Model

“…Currently, there are few biomarkers allowing early detection of gliomas. Several studies using multiparametric MRI texture analysis, 86 circulating biomarkers, 87 or micro RNAs 88 have shown their usefulness as biomarkers for patients with glioma. Maleschlijski et al 74 have also described a strategy for metabolic profiling of glioma subtypes from ex vivo HR-MAS spectra.…”