{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:21:40Z","timestamp":1759332100536,"version":"3.41.2"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pleural effusion (PE), frequently encountered in clinical practice, can arise from a variety of underlying conditions. Accurate differential diagnosis of PE is crucial, as treatment and prognosis are heavily dependent on the underlying etiology. However, diagnosing the cause of PE remains challenging, relying on mycobacteriological methods that lack sensitivity and are time-consuming, or on histological examinations that require invasive biopsies. The recent advancements in metagenomic next-generation sequencing (mNGS) have shown promising applications in the diagnosis of infectious diseases. Despite this, there is limited research on the utility of mNGS as a comprehensive diagnostic tool for simultaneously identifying the causes of PE, particularly in cases of tuberculosis or malignancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aimed to assess the efficacy of mNGS in detecting tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE). A total of 35 patients with PE were included, and their PE samples were analyzed using mNGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the participants, 8 were ultimately diagnosed with TPE, and 10 were diagnosed with MPE, with lung adenocarcinoma being the most prevalent pathological type (50%, 5\/10), according to established diagnostic criteria. Additionally, 7 patients were diagnosed with non-infectious PE. However, mNGS identified only 2 cases of TPE and 8 cases of MPE. The sensitivity of mNGS for detecting <jats:italic>Mycobacterium tuberculosis<\/jats:italic> was 25% (2\/8), while the specificity was 100%. For tumor detection, mNGS demonstrated a sensitivity of 80%, a specificity of 92.6%, and an AUC of 0.882.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>mNGS is effective in distinguishing MPE from non-MPE, but is not suitable for diagnosing TPE.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1525100","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T05:16:55Z","timestamp":1742361415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of the metagenomic next-generation sequencing technology to identify the causes of pleural effusion"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhiyun","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanna","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weitao","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhike","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuquan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weinong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuxiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1056\/NEJMra1403503","article-title":"Pleural disease","volume":"378","author":"Feller-Kopman","year":"2018","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3238\/arztebl.2019.0377","article-title":"Pleural effusion in adults-etiology, diagnosis, and treatment","volume":"116","author":"Jany","year":"2019","journal-title":"Dtsch Arztebl Int"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"507","DOI":"10.7326\/0003-4819-77-4-507","article-title":"Pleural effusions: the diagnostic separation of transudates and exudates","volume":"77","author":"Light","year":"1972","journal-title":"Ann Intern Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1084\/jem.20211777","article-title":"Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion","volume":"219","author":"Cai","year":"2022","journal-title":"J Exp Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6690","DOI":"10.1038\/s41467-021-27026-9","article-title":"Single-cell analysis of diverse immune phenotypes in malignant pleural effusion","volume":"12","author":"Huang","year":"2021","journal-title":"Nat Commun"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1164\/rccm.201807-1415ST","article-title":"Management of Malignant Pleural Effusions. An official ATS\/STS\/STR clinical practice guideline","volume":"198","author":"Feller-Kopman","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1378\/chest.06-2063","article-title":"Diagnosis and treatment of tuberculous pleural effusion in 2006","volume":"131","author":"Gopi","year":"2007","journal-title":"Chest"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1790158","DOI":"10.1080\/20013078.2020.1790158","article-title":"Metabolic characteristics of large and small extracellular vesicles from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy","volume":"9","author":"Luo","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1753466618808660","DOI":"10.1177\/1753466618808660","article-title":"Biomarkers in the diagnosis of pleural diseases: a 2018 update","volume":"12","author":"Porcel","year":"2018","journal-title":"Ther Adv Respir Dis"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41564-018-0349-6","article-title":"Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease","volume":"4","author":"Blauwkamp","year":"2019","journal-title":"Nat Microbiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S416","DOI":"10.1093\/cid\/ciaa1516","article-title":"Clinical utility of in-house metagenomic next-generation sequencing for the diagnosis of lower respiratory tract infections and analysis of the host immune response","volume":"71","author":"Chen","year":"2020","journal-title":"Clin Infect Dis"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1007\/s11427-019-1614-0","article-title":"Distinct lung microbial community states in patients with pulmonary tuberculosis","volume":"63","author":"Hu","year":"2020","journal-title":"Sci China Life Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/0002-9343(77)90154-1","article-title":"Carcinomatous involvement of the pleura: an analysis of 96 patients","volume":"63","author":"Chernow","year":"1977","journal-title":"Am J Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12890-015-0025-z","article-title":"Important prognostic factors for survival in patients with malignant pleural effusion","volume":"15","author":"Zamboni","year":"2015","journal-title":"BMC Pulm Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13073-021-00912-z","article-title":"Detection of cryptogenic malignancies from metagenomic whole genome sequencing of body fluids","volume":"13","author":"Gu","year":"2021","journal-title":"Genome Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"103639","DOI":"10.1016\/j.ebiom.2021.103639","article-title":"Metagenomic next-generation sequencing to identify pathogens and cancer in lung biopsy tissue","volume":"73","author":"Guo","year":"2021","journal-title":"EBioMedicine"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1111\/jam.15003","article-title":"A proof-of-concept study of an automated solution for clinical metagenomic next-generation sequencing","volume":"131","author":"Luan","year":"2021","journal-title":"J Appl Microbiol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"892087","DOI":"10.3389\/fcimb.2022.892087","article-title":"Simultaneous detection of pathogens and tumors in patients with suspected infections by next-generation sequencing","volume":"12","author":"Su","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with kraken 2","volume":"20","author":"Wood","year":"2019","journal-title":"Genome Biol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1093\/clinchem\/hvac024","article-title":"Optimized sequencing adaptors enable rapid and real-time metagenomic identification of pathogens during runtime of sequencing","volume":"68","author":"Zhang","year":"2022","journal-title":"Clin Chem"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s12931-023-02597-x","article-title":"Metagenomics for the microbiological diagnosis of hospital-acquired pneumonia and ventilator-associated pneumonia (HAP\/VAP) in intensive care unit (ICU): a proof-of-concept study","volume":"24","author":"Heitz","year":"2023","journal-title":"Respir Res"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41576-019-0113-7","article-title":"Clinical metagenomics","volume":"20","author":"Chiu","year":"2019","journal-title":"Nat Rev Genet"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/cas.13837","article-title":"Next generation sequencing-based gene panel tests for the management of solid tumors","volume":"110","author":"Nagahashi","year":"2019","journal-title":"Cancer Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.jinf.2017.10.012","article-title":"Metagenomic analysis identified co-infection with human rhinovirus C and bocavirus 1 in an adult suffering from severe pneumonia","volume":"76","author":"Li","year":"2018","journal-title":"J Infect"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1056\/NEJMoa1803396","article-title":"Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis","volume":"380","author":"Wilson","year":"2019","journal-title":"N Engl J Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1458316","DOI":"10.3389\/fcimb.2024.1458316","article-title":"Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases","volume":"14","author":"Zhao","year":"2024","journal-title":"Front Cell Infect Microbiol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12931-023-02654-5","article-title":"Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia","volume":"25","author":"Wang","year":"2024","journal-title":"Respir Res"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1000667","DOI":"10.1371\/journal.pcbi.1000667","article-title":"A primer on metagenomics","volume":"6","author":"Wooley","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1016\/S2666-5247(22)00359-7","article-title":"WHO's global tuberculosis report 2022","volume":"4","author":"Bagcchi","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref32","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":"ref33","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0140-6736(19)30024-8","article-title":"Building a tuberculosis-free world: the lancet commission on tuberculosis","volume":"393","author":"Reid","year":"2019","journal-title":"Lancet"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ijid.2022.12.005","article-title":"Extrapulmonary tuberculosis in China: a national survey","volume":"128","author":"Li","year":"2023","journal-title":"Int J Infect Dis"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"106607","DOI":"10.1016\/j.rmed.2021.106607","article-title":"Diagnosis of tuberculous pleural effusions: a review","volume":"188","author":"Lo Cascio","year":"2021","journal-title":"Respir Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1111\/crj.12900","article-title":"Pleural tuberculosis: A concise clinical review","volume":"12","author":"Shaw","year":"2018","journal-title":"Clin Respir J"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/j.1440-1843.2010.01723.x","article-title":"Update on tuberculous pleural effusion","volume":"15","author":"Light","year":"2010","journal-title":"Respirology"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1684\/abc.2016.1201","article-title":"Biological markers in the diagnosis of tuberculous pleural effusion","volume":"75","author":"Mollo","year":"2017","journal-title":"Ann Biol Clin (Paris)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e0247321","DOI":"10.1128\/spectrum.02473-21","article-title":"Improving suspected pulmonary infection diagnosis by Bronchoalveolar lavage fluid metagenomic next-generation sequencing: a multicenter retrospective study","volume":"10","author":"Jin","year":"2022","journal-title":"Microbiol Spectr"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ijid.2020.12.063","article-title":"Tuberculosis diagnosis by metagenomic next-generation sequencing on Bronchoalveolar lavage fluid: a cross-sectional analysis","volume":"104","author":"Liu","year":"2021","journal-title":"Int J Infect Dis"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1111\/j.1365-3083.2009.02294.x","article-title":"Peripheral immune response in pulmonary tuberculosis","volume":"70","author":"Aktas","year":"2009","journal-title":"Scand J Immunol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00408-009-9165-3","article-title":"Tuberculous pleural effusion","volume":"187","author":"Porcel","year":"2009","journal-title":"Lung"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3389\/fcimb.2019.00351","article-title":"Clinical evaluation of diagnosis efficacy of active Mycobacterium tuberculosis complex infection via metagenomic next-generation sequencing of direct clinical samples","volume":"9","author":"Zhou","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1001\/jamaneurol.2021.3088","article-title":"Detection of neoplasms by metagenomic next-generation sequencing of cerebrospinal fluid","volume":"78","author":"Gu","year":"2021","journal-title":"JAMA Neurol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1093\/ejcts\/ezy258","article-title":"ERS\/EACTS statement on the management of malignant pleural effusions","volume":"55","author":"Bibby","year":"2019","journal-title":"Eur J Cardiothorac Surg"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2147\/CMAR.S95663","article-title":"Management of malignant pleural effusion: challenges and solutions","volume":"9","author":"Penz","year":"2017","journal-title":"Cancer Manag Res"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.path.2018.05.003","article-title":"Updates in effusion cytology","volume":"11","author":"Lepus","year":"2018","journal-title":"Surg Pathol Clin"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"490","DOI":"10.3390\/medicina55080490","article-title":"Malignant pleural effusion and its current management: a review","volume":"55","author":"Skok","year":"2019","journal-title":"Medicina (Kaunas)"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"8092","DOI":"10.3892\/ol.2017.7226","article-title":"Diagnostic value of medical thoracoscopy in malignant pleural effusion induced by non-Hodgkin's lymphoma","volume":"14","author":"Wang","year":"2017","journal-title":"Oncol Lett"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1378\/chest.125.4.1546","article-title":"Pleural effusions in hematologic malignancies","volume":"125","author":"Alexandrakis","year":"2004","journal-title":"Chest"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.3389\/fcimb.2023.1243441","article-title":"Diagnostic accuracy and microbial profiles of tuberculous pleurisy: a comparative study of metagenomic next generation sequencing and Gene Xpert Mycobacterium tuberculosis","volume":"13","author":"Huang","year":"2023","journal-title":"Front Cell Infect Microbiol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1525100\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T05:16:57Z","timestamp":1742361417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1525100\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":51,"alternative-id":["10.3389\/fmed.2025.1525100"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1525100","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"article-number":"1525100"}}