{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:13:14Z","timestamp":1785467594206,"version":"3.56.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1125946","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T16:57:21Z","timestamp":1678121841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Qiang","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huquan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengchun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liehua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1907426","DOI":"10.1155\/2019\/1907426","article-title":"Serum exosomal miRNAs are associated with active pulmonary tuberculosis","volume":"2019","author":"Alipoor","year":"2019","journal-title":"Dis. Markers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/genes8090234","article-title":"Circulating microRNAs and bioinformatics tools to discover novel diagnostic biomarkers of pediatric diseases","volume":"8","author":"Baldassarre","year":"2017","journal-title":"Genes (Basel)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/0092-8674(81)90501-8","article-title":"Mutations that lead to reiterations in the cell lineages of c. elegans","volume":"24","author":"Chalfie","year":"1981","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.836636","article-title":"Comparison of data normalization strategies for array-based MicroRNA profiling experiments and identification and validation of circulating MicroRNAs as endogenous controls in hypertension","volume":"13","author":"Chekka","year":"2022","journal-title":"Front. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3660","DOI":"10.7150\/jca.27124","article-title":"MiR-543 promotes cell proliferation and metastasis of renal cell carcinoma by targeting dickkopf 1 through the wnt\/beta-catenin signaling pathway","volume":"9","author":"Chen","year":"2018","journal-title":"J. Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00118","article-title":"Circulating microRNAs as potential biomarkers of infectious disease","volume":"8","author":"Correia","year":"2017","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1302\/0301-620X.100B4.BJJ-2017-1040.R1","article-title":"Spinal tuberculosis: Review of current management","author":"Dunn","year":"2018","journal-title":"Bone Joint J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1179\/2045772311Y.0000000023","article-title":"Spinal tuberculosis: A review","volume":"34","author":"Garg","year":"2011","journal-title":"J. Spinal Cord Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.canep.2012.04.001","article-title":"Analysis of serum microRNAs (miR-26a-2*, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma","volume":"36","author":"Hauser","year":"2012","journal-title":"Cancer Epidemiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/aps.2011.189","article-title":"Sirt1 overexpression protects murine osteoblasts against TNF-alpha-induced injury in vitro by suppressing the NF-kappaB signaling pathway","volume":"33","author":"Huang","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"B11","doi-asserted-by":"publisher","first-page":"W180","DOI":"10.1093\/nar\/gky509","article-title":"TAM 2.0: tool for MicroRNA set analysis","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3892\/ijo.2014.2469","article-title":"Differential expression of miRNAs in colon cancer between African and Caucasian americans: implications for cancer racial health disparities","volume":"45","author":"Li","year":"2014","journal-title":"Int. J. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"5075","DOI":"10.3892\/mmr.2019.10762","article-title":"Identification of dysregulated serum miR-508-3p and miR-885-5p as potential diagnostic biomarkers of clear cell renal carcinoma","volume":"20","author":"Liu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"191.e1","DOI":"10.1016\/j.ajog.2014.08.028","article-title":"MicroRNAs in endometrial cancers from black and white patients","volume":"212","author":"Maxwell","year":"2015","journal-title":"Am. J. Obstetr. Gynecol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3171\/jns.1995.83.2.0243","article-title":"Spinal tuberculosis: a diagnostic and management challenge","volume":"83","author":"Nussbaum","year":"1995","journal-title":"J. Neurosurg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41413-018-0018-7","article-title":"YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating beta-catenin signaling","volume":"6","author":"Pan","year":"2018","journal-title":"Bone Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1002\/1097-0258(20000830)19:16<2115::AID-SIM529>3.0.CO;2-M","article-title":"Measuring the effectiveness of diagnostic markers in the presence of measurement error through the use of ROC curves","volume":"19","author":"Reiser","year":"2000","journal-title":"Stat. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1080\/09168451.2019.1591260","article-title":"MicroRNA-543 promotes cell invasion and impedes apoptosis in pituitary adenoma via activating the wnt\/beta-catenin pathway by negative regulation of Smad7","volume":"83","author":"Shen","year":"2019","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.juro.2014.07.010","article-title":"Circulating serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as biomarkers in patients with testicular germ cell cancer","volume":"193","author":"Syring","year":"2015","journal-title":"J. Urol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1158\/0008-5472.CAN-17-1947","article-title":"Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast CancerShort noncoding RNAs in TNBC disparities","volume":"78","author":"Telonis","year":"2018","journal-title":"Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01274","article-title":"Circulating MicroRNAs: Potential and emerging biomarkers for diagnosis of human infectious diseases","volume":"7","author":"Verma","year":"2016","journal-title":"Front. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004923","article-title":"Trends of spinal tuberculosis research (1994\u20132015): A bibliometric study","volume":"95","author":"Wang","year":"2016","journal-title":"Medicine"},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-21736-9","volume-title":"All of statistics: A concise course in statistical inference","author":"Wasserman","year":"2004"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1373\/clinchem.2010.147405","article-title":"The microRNA spectrum in 12 body fluids","volume":"56","author":"Weber","year":"2010","journal-title":"Clin. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3978\/j.issn.2072-1439.2012.05.08","article-title":"MicroRNA from tuberculosis RNA: A bioinformatics study","volume":"4","author":"Wiwanitkit","year":"2012","journal-title":"J. Thorac. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"344","DOI":"10.4149\/neo_2020_190517N441","article-title":"MicroRNA-506-3p inhibits proliferation and promotes apoptosis in ovarian cancer cell via targeting SIRT1\/AKT\/FOXO3a signaling pathway","volume":"67","author":"Xia","year":"2020","journal-title":"Neoplasma"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5646","DOI":"10.1002\/jcb.26743","article-title":"Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p","volume":"119","author":"Yang","year":"2018","journal-title":"J. Cell Biochem."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081076","article-title":"Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis","volume":"8","author":"Zhang","year":"2013","journal-title":"PloS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1125946\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T16:57:25Z","timestamp":1678121845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1125946\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,28]]},"references-count":28,"alternative-id":["10.3389\/fcimb.2023.1125946"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1125946","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,28]]},"article-number":"1125946"}}