Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

Junseong Kim,Kyung Eun Lee,Hyejon Lee,Sunghyun Kim,Sang-Nae Cho,Eunsol Ahn,Min-A Je,Heechul Park,Eun Ju Lee,Hyunwoo Jin,Sung-Bae Park,Jiyoung Lee,Jungho Kim,Bora Sim,Young Ae Kang

doi:10.3390/diagnostics12020369

Abstract

Early diagnosis increases the treatment success rate for active tuberculosis (ATB) and decreases mortality. MicroRNAs (miRNAs) have been studied as blood-based markers of several infectious diseases. We performed miRNA profiling to identify differentially expressed (DE) miRNAs using whole blood samples from 10 healthy controls (HCs), 15 subjects with latent tuberculosis infection (LTBI), and 12 patients with ATB, and investigated the expression of the top six miRNAs at diagnosis and over the treatment period in addition to performing miRNA-target gene network and gene ontology analyses. miRNA profiling identified 84 DE miRNAs in patients with ATB, including 80 upregulated and four downregulated miRNAs. Receiver operating characteristic curves of the top six miRNAs exhibited excellent distinguishing efficiency with an area under curve (AUC) value > 0.85. Among them, miR-199a-3p and miR-6886-3p can differentiate between ATB and LTBI. Anti-TB treatment restored the levels of miR-199b-3p, miR-199a-3p, miR-16-5p, and miR-374c-5p to HC levels. Furthermore, 108 predicted target genes were related to the regulation of cellular amide metabolism, intrinsic apoptotic signaling, translation, transforming growth factor beta receptor signaling, and cysteine-type endopeptidase activity. The DE miRNAs identified herein are potential biomarkers for diagnosis and therapeutic monitoring in ATB.

Highlights

Tuberculosis (TB) is a fatal infectious disease caused by Mycobacterium tuberculosis (MTB) infection [1]
Of all patients infected with MTB, about 5% of them will have active tuberculosis (ATB), and about 95% will develop latent TB infection (LTBI)
MiRNA expression profiling was performed using 37 blood samples consisting of 12 ATB, 15 LTBI, and 10 healthy control (HC) samples to identify potential miRNAs for TB diagnosis and treatment monitoring

Summary

Introduction

Tuberculosis (TB) is a fatal infectious disease caused by Mycobacterium tuberculosis (MTB) infection [1]. According to the World Health Organization (WHO), there were approximately 10 million new cases and 1.2 million deaths attributed to TB worldwide in 2019 [2]. 85% of MTB infections occur in the lungs but infections can spread and affect multiple organs [1]. According to a WHO report in 2021, TB is the most powerful single pathogen to have emerged before coronavirus disease 2019 (COVID-19) and about one-quarter of the world’s population is infected with MTB. Of all patients infected with MTB, about 5% of them will have active tuberculosis (ATB), and about 95% will develop latent TB infection (LTBI). It is likely that they will develop ATB during their lifetime [3]

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