title: Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer.
abstract: 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-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. 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 (pPFS = 7.92 × 10(-6) and pOS = 5.27 × 10(-5)) and validation studies (pPFS = 3.66 × 10(-4) and pOS = 1.43 × 10(-4)). 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 = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients.
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Cike
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.|National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.affiliation: Division of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ćuk
authors.affiliation: Division of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Eilber
authors.affiliation: Division of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Muhabbet
authors.initials: M
authors.lastname: Celik
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.|National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Modugno
authors.affiliation: Hi-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH, Heidelberg, Germany.|Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Heil
authors.affiliation: Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Dharanija
authors.initials: D
authors.lastname: Madhavan
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.|National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Nees
authors.affiliation: Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schott
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.affiliation: Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.|National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Division of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rongxi
authors.initials: R
authors.lastname: Yang
authors.affiliation: Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Molecular Biology of Breast Cancer, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D053208:Kaplan-Meier Estimate; D009362:Neoplasm Metastasis; D063868:Patient Outcome Assessment; D011379:Prognosis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D006820:Hyaluronic Acid
keywords: biomarker; hyaluronic acid; metastatic breast cancer; plasma; prognosis