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

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 samp...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/12/2/369
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author 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
author_facet 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
author_sort Junseong Kim
collection DOAJ
description 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.
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spelling doaj.art-1ac7e46d59694599b05f23062ae3501a2023-11-23T19:30:54ZengMDPI AGDiagnostics2075-44182022-02-0112236910.3390/diagnostics12020369Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active TuberculosisJunseong Kim0Heechul Park1Sung-Bae Park2Eun Ju Lee3Min-A Je4Eunsol Ahn5Bora Sim6Jiyoung Lee7Hyunwoo Jin8Kyung Eun Lee9Sang-Nae Cho10Young Ae Kang11Hyejon Lee12Sunghyun Kim13Jungho Kim14Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaClinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, KoreaDepartment of Microbiology, Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03772, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaClinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, KoreaDivision 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, KoreaClinical Vaccine Research Section, International Tuberculosis Research Center, Seoul 03772, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaDepartment of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, KoreaEarly 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.https://www.mdpi.com/2075-4418/12/2/369tuberculosislatent tuberculosis infectionbiomarkersmicroRNAs
spellingShingle 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
Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
Diagnostics
tuberculosis
latent tuberculosis infection
biomarkers
microRNAs
title Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
title_full Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
title_fullStr Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
title_full_unstemmed Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
title_short Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis
title_sort identification of micrornas as potential blood based biomarkers for diagnosis and therapeutic monitoring of active tuberculosis
topic tuberculosis
latent tuberculosis infection
biomarkers
microRNAs
url https://www.mdpi.com/2075-4418/12/2/369
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