{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:29:30Z","timestamp":1781076570835,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Advanced Biomass R&amp;D Center of Korea","award":["2011-0031353"],"award-info":[{"award-number":["2011-0031353"]}]},{"name":"the National Research Foundation of Korea funded by the Ministry of Education","award":["NRF-2013R1A1A2059103"],"award-info":[{"award-number":["NRF-2013R1A1A2059103"]}]},{"name":"the Ministry of Health &amp; Welfare","award":["HI14C2285"],"award-info":[{"award-number":["HI14C2285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diagnosing Behcet\u2019s disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography\/time-of-flight\u2013mass spectrometry (GC\/TOF\u2212MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC\/TOF\u2212MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC\/TOF\u2212MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC\/TOF\u2212MS.<\/jats:p>","DOI":"10.3390\/ijms18112309","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T04:43:13Z","timestamp":1509684193000},"page":"2309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet\u2019s Disease by Gas Chromatography\/Time-of-Flight\u2212Mass Spectrometry"],"prefix":"10.3390","volume":"18","author":[{"given":"Joong","family":"Ahn","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Police Hospital, Seoul 05715, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhwan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-8668","authenticated-orcid":false,"given":"Kyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon-Suk","family":"Cha","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrrheum.2012.156","article-title":"Differential diagnosis and management of Behcet syndrome","volume":"9","author":"Ambrose","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1056\/NEJM199910213411707","article-title":"Behcet\u2019s disease","volume":"341","author":"Sakane","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493015","DOI":"10.1155\/2012\/493015","article-title":"Pathophysiology of the Behcet\u2019s disease","volume":"2012","author":"Tursen","year":"2012","journal-title":"Pathol. Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrrheum.2016.1","article-title":"Metabolomics in rheumatic diseases: Desperately seeking biomarkers","volume":"12","author":"Guma","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ahn, J.K., Kim, S., Kim, J., Hwang, J., Kim, K.H., and Cha, H.S. (2015). A Comparative metabolomic evaluation of Behcet\u2019s disease with arthritis and seronegative arthritis using synovial fluid. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135856"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ahn, J.K., Kim, J., Hwang, J., Song, J., Kim, K.H., and Cha, H.S. (2017). Potential metabolomic biomarkers for reliable diagnosis of Behcet\u2019s disease using gas chromatography with time-of-flight mass spectrometry. Jt. Bone Spine.","DOI":"10.1136\/annrheumdis-2017-eular.3104"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35309","DOI":"10.1038\/srep35309","article-title":"NMR based serum metabolomics reveals a distinctive signature in patients with Lupus Nephritis","volume":"6","author":"Guleria","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1002\/art.37921","article-title":"Metabolic profiling predicts response to anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis","volume":"65","author":"Kapoor","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Van Wietmarschen, H.A., Dai, W., van der Kooij, A.J., Reijmers, T.H., Schroen, Y., Wang, M., Xu, Z., Wang, X., Kong, H., and Xu, G. (2012). Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044331"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s13075-016-1139-2","article-title":"Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles","volume":"18","author":"Wang","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrrheum.2017.49","article-title":"Immunometabolism in early and late stages of rheumatoid arthritis","volume":"13","author":"Weyand","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/nrrheum.2017.43","article-title":"Immunometabolism in systemic lupus erythematosus","volume":"13","author":"Morel","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrrheum.2017.37","article-title":"Metabolic regulation of inflammation","volume":"13","author":"Gaber","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Villas-Boas, S.G., Roessner, U., Hansen, M.A.E., Smedsgaard, J., and Nielsen, J. (2007). Metabolomics in humans and other mammals. Metabolome Analysis: An Introduction, Wiley-Interscience.","DOI":"10.1002\/0470105518"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35010","DOI":"10.1038\/srep35010","article-title":"Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging","volume":"6","author":"Xu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/j.1346-8138.2004.tb00641.x","article-title":"The significance of serum nitric oxide levels in Behcet\u2019s disease and recurrent aphthous stomatitis","volume":"31","author":"Yildirim","year":"2004","journal-title":"J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.4103\/0019-5154.70667","article-title":"Assessment of serum homocysteine, endothelin-1, and nitric oxide levels in Behcet\u2019s disease","volume":"55","author":"Hodeib","year":"2010","journal-title":"Indian J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0009-8981(02)00278-4","article-title":"The activities of serum adenosine deaminase and xanthine oxidase enzymes in Behcet\u2019s disease","volume":"325","author":"Sogut","year":"2002","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.niox.2007.07.001","article-title":"Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle","volume":"17","author":"Flam","year":"2007","journal-title":"Nitric Oxide"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/00124743-200102000-00003","article-title":"Serum and urine nitrite and citrulline levels among patients with systemic lupus erythematosus: A possible addition to activity parameters?","volume":"7","author":"Wanchu","year":"2001","journal-title":"J. Clin. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.autrev.2014.11.009","article-title":"Behcet\u2019s syndrome patients exhibit specific microbiome signature","volume":"14","author":"Consolandi","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bouatra, S., Aziat, F., Mandal, R., Guo, A.C., Wilson, M.R., Knox, C., Bjorndahl, T.C., Krishnamurthy, R., Saleem, F., and Liu, P. (2013). The human urine metabolome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073076"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1139\/apnm-2015-0452","article-title":"Whole-body fat oxidation increases more by prior exercise than overnight fasting in elite endurance athletes","volume":"41","author":"Edin","year":"2016","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Priori, R., Casadei, L., Valerio, M., Scrivo, R., Valesini, G., and Manetti, C. (2015). (1)H-NMR-Based metabolomic study for identifying serum profiles associated with the response to etanercept in patients with rheumatoid arthritis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138537"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"International Study Group for Behcet\u2019s Disease (1990). Criteria for diagnosis of Behcet\u2019s disease. Lancet, 335, 1078\u20131080.","DOI":"10.1016\/0140-6736(90)92643-V"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/nprot.2011.375","article-title":"Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry","volume":"6","author":"Chan","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1746-4811-4-7","article-title":"High quality metabolomic data for Chlamydomonas reinhardtii","volume":"4","author":"Lee","year":"2008","journal-title":"Plant Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10038","DOI":"10.1021\/ac9019522","article-title":"FiehnLib: Mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography\/mass spectrometry","volume":"81","author":"Kind","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W71","DOI":"10.1093\/nar\/gkq329","article-title":"MSEA: A web-based tool to identify biologically meaningful patterns in quantitative metabolomic data","volume":"38","author":"Xia","year":"2010","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:49:12Z","timestamp":1760208552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":29,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["ijms18112309"],"URL":"https:\/\/doi.org\/10.3390\/ijms18112309","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]}}}