{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:09:27Z","timestamp":1790262567824,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dietmar-Hopp Foundation, the University Hospital of Heidelberg, the Helmholtz Society, the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases, (IFP-Project I.2)"},{"name":"China Scholarship Council (CSC; for a 4-year PhD program; C.P.)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5\u2010year follow\u2010up and validated in an independent validation cohort of 334 patients with 5\u2010year follow\u2010up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery <jats:italic>(p<\/jats:italic><jats:sub>PFS<\/jats:sub>\u2009=\u20097.92 \u00d7 10<jats:sup>\u22126<\/jats:sup> and <jats:italic>p<\/jats:italic><jats:sub>OS<\/jats:sub>\u2009=\u20095.27 \u00d7 10<jats:sup>\u22125<\/jats:sup>) and validation studies (<jats:italic>p<\/jats:italic><jats:sub>PFS<\/jats:sub>\u2009=\u20093.66 \u00d7 10<jats:sup>\u22124<\/jats:sup> and <jats:italic>p<\/jats:italic><jats:sub>OS<\/jats:sub>\u2009=\u20091.43 \u00d7 10<jats:sup>\u22124<\/jats:sup>). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC\u2009=\u20090.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients.<\/jats:p>","DOI":"10.1002\/ijc.29975","type":"journal-article","created":{"date-parts":[[2015,12,19]],"date-time":"2015-12-19T15:54:43Z","timestamp":1450540483000},"page":"2499-2509","source":"Crossref","is-referenced-by-count":33,"title":["Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer"],"prefix":"10.1002","volume":"138","author":[{"given":"Cike","family":"Peng","sequence":"first","affiliation":[{"name":"Molecular Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Wallwiener","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"},{"name":"National Center for Tumor Diseases, University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Division of Genetic Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"\u0106uk","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Eilber","sequence":"additional","affiliation":[{"name":"Division of Genetic Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhabbet","family":"Celik","sequence":"additional","affiliation":[{"name":"Division of Genetic Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Modugno","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"},{"name":"National Center for Tumor Diseases, University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Trumpp","sequence":"additional","affiliation":[{"name":"Hi\u2010STEM\u2010Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH Heidelberg Germany"},{"name":"Division of Stem Cells and Cancer German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Heil","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Marm\u00e9","sequence":"additional","affiliation":[{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharanija","family":"Madhavan","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Nees","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"},{"name":"National Center for Tumor Diseases, University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Riethdorf","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology University Hospital Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pantel","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology University Hospital Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schneeweiss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"},{"name":"National Center for Tumor Diseases, University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Chang\u2010Claude","sequence":"additional","affiliation":[{"name":"Division of Genetic Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Burwinkel","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology German Cancer Research Center (DKFZ) Heidelberg Germany"},{"name":"Molecular Biology of Breast Cancer Department of Obstetrics and Gynecology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-28160-0_18"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl155"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2576"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-138"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2382-0"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23825"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.165068"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0879-y"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.07.001"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.027"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10911-010-9174-0"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59349-9_13"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20065"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602418"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2008.03.005"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1997.00171.x"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22349"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63636-X"},{"key":"e_1_2_15_20_1","first-page":"1101","article-title":"Role of hyaluronan and hyaluronan synthase in endometrial cancer","volume":"13","author":"Yabushita H","year":"2005","journal-title":"Oncol Rep"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2011.07.018"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910460309"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2230-2"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365518809088758"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1695"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwq145"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040766"},{"key":"e_1_2_15_28_1","first-page":"295","article-title":"Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes","volume":"43","author":"Millner LM","year":"2013","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.6462"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1391"},{"key":"e_1_2_15_31_1","first-page":"428","article-title":"Hyaluronan on the surface of tumor cells is correlated with metastatic behavior","volume":"55","author":"Zhang L","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-012-0404-8"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2006.05.009"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506740200"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2804-7"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.7A7270.2007"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2013.73"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070535"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0450"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.7754\/Clin.Lab.2013.130413"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms131012925"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29975","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29975","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.29975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T14:52:51Z","timestamp":1695567171000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.29975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,16]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,5,15]]}},"alternative-id":["10.1002\/ijc.29975"],"URL":"https:\/\/doi.org\/10.1002\/ijc.29975","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,16]]}}}