A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB)...

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Main Authors: Qiang Liang, Weidong Jin, Zhigang Huang, Huquan Yin, Shengchun Liu, Liehua Liu, Xiangwei Song, Zili Wang, Jun Fei
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125946/full
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author Qiang Liang
Qiang Liang
Weidong Jin
Zhigang Huang
Huquan Yin
Shengchun Liu
Liehua Liu
Xiangwei Song
Zili Wang
Zili Wang
Jun Fei
author_facet Qiang Liang
Qiang Liang
Weidong Jin
Zhigang Huang
Huquan Yin
Shengchun Liu
Liehua Liu
Xiangwei Song
Zili Wang
Zili Wang
Jun Fei
author_sort Qiang Liang
collection DOAJ
description Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden’s J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.
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spelling doaj.art-bc3bff9f03fb419bbeac6acef4969a0b2023-02-28T06:30:59ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-02-011310.3389/fcimb.2023.11259461125946A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosisQiang Liang0Qiang Liang1Weidong Jin2Zhigang Huang3Huquan Yin4Shengchun Liu5Liehua Liu6Xiangwei Song7Zili Wang8Zili Wang9Jun Fei10Department of Spinal Surgery, Yantai Yuhuangding Hospital, Yantai, ChinaDepartment of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaDepartment of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaDepartment of Orthopedics, The Third People’s Hospital of Shenzhen, Shenzhen, ChinaDepartment of Biochemistry, Inteliex Biomedical Corp, Tampa, FL, United StatesDepartment of Orthopedics, The Tenth People’s Hospital of Shenyang, Shenyang, ChinaDepartment of Spine Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopaedics, First Affiliated Hospital of Xinxiang Medical College, Weihui, ChinaDepartment of Spinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, ChinaDepartment of Spine Surgery, Xi’an International Medical Center Hospital Affiliated to Northwest University, Xi’an, Shaanxi, ChinaDepartment of Orthopedics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaAccurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden’s J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125946/fullmicroRNAsspinal tuberculosisdiagnostic modeldiscriminationbiomarker
spellingShingle Qiang Liang
Qiang Liang
Weidong Jin
Zhigang Huang
Huquan Yin
Shengchun Liu
Liehua Liu
Xiangwei Song
Zili Wang
Zili Wang
Jun Fei
A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
Frontiers in Cellular and Infection Microbiology
microRNAs
spinal tuberculosis
diagnostic model
discrimination
biomarker
title A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
title_full A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
title_fullStr A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
title_full_unstemmed A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
title_short A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
title_sort plasma 3 marker microrna biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis
topic microRNAs
spinal tuberculosis
diagnostic model
discrimination
biomarker
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125946/full
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