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

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.

Keywords

• tuberculosis
• latent tuberculosis infection
• biomarkers
• microRNAs