Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis

Abstract

Circular RNAs (circRNAs) are a class of novel RNAswith important biological functions, and aberrant expression of circRNAs has been implicated in human diseases. However, the feasibility of using blood circRNAs as disease biomarkers is largely unknown. Methods: We explored the potential of using human peripheral blood mononuclear cell (PBMC) circRNAs as marker molecules to diagnose active pulmonary tuberculosis (TB). Findings: First, we demonstrated that circRNAs are widely expressed in human PBMCs and that many are abundant enough to be detected. Second, we found that the magnitude of PBMC circRNAs in TB patients was higher than that in the paired healthy controls. Comparedwith host linear transcripts, the circRNAs with in several pathways are disproportionately upregulated in active TB patients, including "Cytokine-cytokine receptor interaction", "Chemokine signaling pathway", "Neurotrophin signaling pathway", and "Bacterial invasion of epithelial cells". Based on the differentially expressed circRNAs within these pathways, we developed a PBMC circRNAbasedmolecular signature differentiating active TB patients fromhealthy controls. We validated the classification power of the PBMC circRNA signature in an independent cohort with the area under the receiver operating characteristic curve (AUC) at 0.946. Interpretation: Our results suggest that PBMC circRNAs are potentially reliable marker molecules in TB diagnosis. (c) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.