A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis

Abstract Background Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify bio...

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Main Authors: Harinisri Gunasekaran, Pavithra Sampath, Kannan Thiruvengadam, Muniyandi Malaisamy, Rathinasabapati Ramasamy, Uma Devi Ranganathan, Ramalingam Bethunaickan
Format: Article
Language:English
Published: BMC 2024-04-01
Series:BMC Infectious Diseases
Subjects:
Online Access:https://doi.org/10.1186/s12879-024-09232-0
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author Harinisri Gunasekaran
Pavithra Sampath
Kannan Thiruvengadam
Muniyandi Malaisamy
Rathinasabapati Ramasamy
Uma Devi Ranganathan
Ramalingam Bethunaickan
author_facet Harinisri Gunasekaran
Pavithra Sampath
Kannan Thiruvengadam
Muniyandi Malaisamy
Rathinasabapati Ramasamy
Uma Devi Ranganathan
Ramalingam Bethunaickan
author_sort Harinisri Gunasekaran
collection DOAJ
description Abstract Background Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). Methods Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. Results After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. Conclusion miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. Systematic review registration PROSPERO (CRD42022302729).
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spelling doaj.art-812cafd46e8f461fb9e5796710b867662024-04-21T11:10:20ZengBMCBMC Infectious Diseases1471-23342024-04-0124111210.1186/s12879-024-09232-0A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosisHarinisri Gunasekaran0Pavithra Sampath1Kannan Thiruvengadam2Muniyandi Malaisamy3Rathinasabapati Ramasamy4Uma Devi Ranganathan5Ramalingam Bethunaickan6Department of Immunology, ICMR-National Institute for Research in TuberculosisDepartment of Immunology, ICMR-National Institute for Research in TuberculosisDepartment of Epidemiology Statistics, ICMR-National Institute for Research in TuberculosisDepartment of Health Economics, ICMR-National Institute for Research in TuberculosisLibrary and Information Center, ICMR-National Institute for Research in TuberculosisDepartment of Immunology, ICMR-National Institute for Research in TuberculosisDepartment of Immunology, ICMR-National Institute for Research in TuberculosisAbstract Background Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). Methods Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. Results After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. Conclusion miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. Systematic review registration PROSPERO (CRD42022302729).https://doi.org/10.1186/s12879-024-09232-0TuberculosismicroRNABiomarkermiR-197miR-144TB diagnosis
spellingShingle Harinisri Gunasekaran
Pavithra Sampath
Kannan Thiruvengadam
Muniyandi Malaisamy
Rathinasabapati Ramasamy
Uma Devi Ranganathan
Ramalingam Bethunaickan
A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
BMC Infectious Diseases
Tuberculosis
microRNA
Biomarker
miR-197
miR-144
TB diagnosis
title A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
title_full A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
title_fullStr A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
title_full_unstemmed A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
title_short A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis
title_sort systematic review and meta analysis of circulating serum and plasma micrornas in tb diagnosis
topic Tuberculosis
microRNA
Biomarker
miR-197
miR-144
TB diagnosis
url https://doi.org/10.1186/s12879-024-09232-0
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