MicroRNAs as diagnostic biomarkers for Tuberculosis: A systematic review and meta- analysis

Abstract

BackgroundThe early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to Mycobacterium tuberculosis (Mtb).MethodsPubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.ResultsWe retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.ConclusionmiRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance. Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

“…Moreover, miR-29a-3p, the most highly expressed miRNA in latent TB patients, can suppress the host’s immune response, decrease IFN-γ level, and escape macrophage phagocytosis through cell apoptosis [ 184 , 185 ]. Recently, a meta-analysis of 21 studies identified miR-29, miR-31, miR-125b, miR-146a, and miR-155 as potential biomarkers for ATB diagnosis [ 186 ]. The overall sensitivity, specificity, and diagnostic odds ratio ( DOR ) for these biomarkers in ATB diagnosis were 87.9% (81.7–92.2%), 81.2% (74.5–86.5%), and 43.1 (20.3–91.3), respectively [ 186 ].…”

“…Recently, a meta-analysis of 21 studies identified miR-29, miR-31, miR-125b, miR-146a, and miR-155 as potential biomarkers for ATB diagnosis [ 186 ]. The overall sensitivity, specificity, and diagnostic odds ratio ( DOR ) for these biomarkers in ATB diagnosis were 87.9% (81.7–92.2%), 81.2% (74.5–86.5%), and 43.1 (20.3–91.3), respectively [ 186 ]. These findings highlight that the differential expression of miRNA during MTB infection may provide insights into developing novel biomarkers to distinguish between ATB and LTBI.…”

miR-29 as diagnostic biomarkers for tuberculosis: a systematic review and meta-analysis

“…Among the upregulated miRNAs, miRNA-29 family (miR-29a, miR-29b, and miR-29c), particularly miR-29a, stands out, as it inhibits immune responses by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells. This mechanism potentially enhances susceptibility to TB ( 13 ). In the context of Mycobacterium tuberculosis infection, the miR-29 family assumes a crucial role in influencing innate and adaptive immunity by exerting an impact on gene expression within macrophages, dendritic cells, B cells, and T cells ( 14 ).…”

In silico analysis of miRNA target genes possibly induced by tuberculosis infection

“…Los miRNA son pequeños RNA reguladores no codificantes que actúan reprimiendo la expresión de proteínas a nivel postranscripcional, y tienen funciones importantes en muchos procesos fisiológicos y fisiopatológicos (10) . Los mecanismos de regulación de los miRNAs, se basan en la complementariedad de secuencias entre el miRNA y el RNAm blanco; si la unión es perfecta resulta en la degradación del RNAm, si la unión es parcial, se reprime la traducción (11) . La deadenilación del RNAm conduce a la inestabilidad y por ende la degradación del RNAm (10) .…”

“…La deadenilación del RNAm conduce a la inestabilidad y por ende la degradación del RNAm (10) . Después de cualquiera de estos mecanismos, se activa la respuesta inmune innata del huésped, con la producción de citocinas y quimiocinas (11) . El desarrollo en las ciencias omicas ha permitido la rápida identificación y caracterización de pequeños RNA no codificantes, los cuales forman parte de un complejo sistema de regulación génica, y se ha encontrado una expresión diferencial de estos en individuos infectados con TB.…”