Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
Junseong Kim,
Heechul Park,
Sung-Bae Park,
Eun Ju Lee,
Min-A Je,
Eunsol Ahn,
Bora Sim,
Jiyoung Lee,
Hyunwoo Jin,
Kyung Eun Lee,
Sang-Nae Cho,
Young Ae Kang,
Hyejon Lee,
Sunghyun Kim,
Jungho Kim
Affiliations
Junseong Kim
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Heechul Park
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Sung-Bae Park
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Eun Ju Lee
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Min-A Je
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Eunsol Ahn
Clinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, Korea
Bora Sim
Department of Microbiology, Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03772, Korea
Jiyoung Lee
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Hyunwoo Jin
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Kyung Eun Lee
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Sang-Nae Cho
Clinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, Korea
Young Ae Kang
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03772, Korea
Hyejon Lee
Clinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, Korea
Sunghyun Kim
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
Jungho Kim
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
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.
