{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:32:27Z","timestamp":1785371547956,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970088"],"award-info":[{"award-number":["81970088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-\u03b3) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups\u2019 levels of HGF expression in peripheral plasma. In female TPE patients aged \u226465 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-\u03b3 were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged \u226465 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993\u20131.000), 100 (95% CI, 89.997\u2013100.000), 96.667 (95% CI, 82.783\u201399.916), 97.222 (95% CI, 83.594\u201399.586), and 100.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1181912","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T16:51:40Z","timestamp":1688662300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion"],"prefix":"10.3389","volume":"14","author":[{"given":"Sheng-Cai","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Yin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Zhong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ming","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1007\/s10096-010-1149-y","article-title":"Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1","volume":"30","author":"Andersen","year":"2011","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1378\/chest.06-2352","article-title":"Pleural tuberculosis in the United States: incidence and drug resistance","volume":"131","author":"Baumann","year":"2007","journal-title":"Chest"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"326","DOI":"10.23736\/S0031-0808.18.03564-4","article-title":"Competence in pleural procedures","volume":"61","author":"Carlucci","year":"2019","journal-title":"Panminerva Med."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1016\/j.ijid.2022.03.011","article-title":"The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to End TB","volume":"124","author":"Chakaya","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4081\/monaldi.2006.582","article-title":"Pleural tuberculosis","volume":"65","author":"Chakrabarti","year":"2006","journal-title":"Monaldi Arch. Chest Dis."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41416-019-0482-x","article-title":"M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma","volume":"121","author":"Dong","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0255321","DOI":"10.1128\/spectrum.02553-21","article-title":"Interleukin 32 as a Potential Marker for Diagnosis of Tuberculous Pleural Effusion","volume":"10","author":"Du","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1016\/S0896-6273(00)80247-0","article-title":"Hepatocyte growth factor\/scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons","volume":"17","author":"Ebens","year":"1996","journal-title":"Neuron"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.3390\/cells10081930","article-title":"Neuroinflammation and Alzheimer's Disease: A Machine Learning Approach to CSF Proteomics","volume":"10","author":"Gaetani","year":"2021","journal-title":"Cells"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/acel.12326","article-title":"How sex and age affect immune responses, susceptibility to infections, and response to vaccination","volume":"14","author":"Giefing-Kr\u00f6ll","year":"2015","journal-title":"Aging Cell"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1148\/radiology.143.1.7063747","article-title":"The meaning and use of the area under a receiver operating characteristic (ROC) curve","volume":"143","author":"Hanley","year":"1982","journal-title":"Radiology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"155218","DOI":"10.1016\/j.cyto.2020.155218","article-title":"Characterization of cytokine profile to distinguish latent tuberculosis from active tuberculosis and healthy controls","volume":"135","author":"He","year":"2020","journal-title":"Cytokine"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1002\/hep.32458","article-title":"C-C motif chemokine ligand 5 confines liver regeneration by down-regulating reparative macrophage-derived hepatocyte growth factor in a forkhead box O 3a-dependent manner","volume":"76","author":"Huang","year":"2022","journal-title":"Hepatology"},{"key":"ref14","first-page":"195","article-title":"Serum hepatocyte growth factor levels in patients with inflammatory lung diseases","volume":"15","author":"Huang","year":"1999","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12890-020-01219-2","article-title":"Influence of age on the diagnostic accuracy of soluble biomarkers for tuberculous pleural effusion: a post hoc analysis","volume":"20","author":"Jiang","year":"2020","journal-title":"BMC Pulm. Med."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0237753","DOI":"10.1371\/journal.pone.0237753","article-title":"The epidemiology of extrapulmonary tuberculosis in China: A large-scale multi-center observational study","volume":"15","author":"Kang","year":"2020","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"118811","DOI":"10.1016\/j.carbpol.2021.118811","article-title":"Hair-growth promoting effect and anti-inflammatory mechanism of Ginkgo biloba polysaccharides","volume":"278","author":"Li","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.it.2013.10.006","article-title":"SeXX matters in immunity","volume":"35","author":"Markle","year":"2014","journal-title":"Trends Immunol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/0092-8674(91)90363-4","article-title":"Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor","volume":"67","author":"Montesano","year":"1991","journal-title":"Cells"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/342440a0","article-title":"Molecular cloning and expression of human hepatocyte growth factor","volume":"342","author":"Nakamura","year":"1989","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3389\/fendo.2018.00503","article-title":"The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes","volume":"9","author":"Oliveira","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3201\/eid2503.180572","article-title":"Epidemiology of Extrapulmonary Tuberculosis among Inpatients, China, 2008-2017","volume":"25","author":"Pang","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"282","DOI":"10.21037\/atm.2016.07.23","article-title":"Advances in the diagnosis of tuberculous pleuritis","volume":"4","author":"Porcel","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1111\/resp.13673","article-title":"Tuberculous pleural effusion","volume":"24","author":"Shaw","year":"2019","journal-title":"Respirology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ccm.2021.08.002","article-title":"Pleural Tuberculosis","volume":"42","author":"Shaw","year":"2021","journal-title":"Clin. Chest Med."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1083\/jcb.123.1.223","article-title":"Scatter factor\/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development","volume":"123","author":"Sonnenberg","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/327239a0","article-title":"Scatter factor is a fibroblast-derived modulator of epithelial cell mobility","volume":"327","author":"Stoker","year":"1987","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1016\/j.ymthe.2018.06.013","article-title":"Therapeutic Effects of Adipose Stem Cells from Diabetic Mice for the Treatment of Type 2 Diabetes","volume":"26","author":"Wang","year":"2018","journal-title":"Mol. Ther."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1159\/000435962","article-title":"Efficacy and safety of diagnostic thoracoscopy in undiagnosed pleural effusions","volume":"90","author":"Wang","year":"2015","journal-title":"Respiration"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1136\/thoraxjnl-2016-209718","article-title":"Diagnostic accuracy of interleukin 27 for tuberculous pleural effusion: two prospective studies and one meta-analysis","volume":"73","author":"Wang","year":"2018","journal-title":"Thorax"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.3760\/cma.j.issn.0366-6999.20130020","article-title":"Combined detections of interleukin 27, interferon-\u03b3, and adenosine deaminase in pleural effusion for diagnosis of tuberculous pleurisy","volume":"126","author":"Wu","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"607","DOI":"10.21037\/atm.2019.09.110","article-title":"The diagnostic utility of pleural markers for tuberculosis pleural effusion","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"808855","DOI":"10.3389\/fphar.2022.808855","article-title":"HGF\/c-Met: A Key Promoter in Liver Regeneration","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/clinchem\/39.4.561","article-title":"Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine","volume":"39","author":"Zweig","year":"1993","journal-title":"Clin. Chem."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1181912\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T16:51:44Z","timestamp":1688662304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1181912\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,6]]},"references-count":34,"alternative-id":["10.3389\/fmicb.2023.1181912"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1181912","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,6]]},"article-number":"1181912"}}