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    European journal of cancer (Oxford, England : 1990). 2016 Jun 8. pii: S0959-8049(16)32116-5. doi: 10.1016/j.ejca.2016.04.018
    Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.
    Hoda MA1,  Dong Y2,  Rozsas A3,  Klikovits T4,  Laszlo V5,  Ghanim B6,  Stockhammer P7,  Ozsvar J8,  Jakopovic M9,  Samarzija M10,  Brcic L11,  Bendek M12,  Szirtes I13,  Reid G14,  Kirschner MB15,  Kao SC16,  Opitz I17,  Weder W18,  Frauenfelder T19,  Nguyen-Kim TD20,  Aigner C21,  Klepetko W22,  van Zandwijk N23,  Berger W24,  Dome B25,  Grusch M26,  Hegedus B27
    Author information
    1Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
    2Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    3Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary.
    4Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    5Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    6Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    7Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    8Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    9University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia.
    10University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia.
    11Medical University of Graz, Institute of Pathology, Graz, Austria.
    12National Koranyi Institute of Pulmonology, Budapest, Hungary.
    132nd Institute of Pathology Semmelweis University, Budapest, Hungary.
    14Asbestos Diseases Research Institute, Sydney, Australia.
    15Asbestos Diseases Research Institute, Sydney, Australia.
    16Asbestos Diseases Research Institute, Sydney, Australia.
    17University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland.
    18University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland.
    19University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland.
    20University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland.
    21Department of Thoracic Surgery, Ruhrlandklinik, Essen, Germany.
    22Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
    23Asbestos Diseases Research Institute, Sydney, Australia.
    24Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
    25Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria.
    26Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
    27Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria; MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: balazs.hegedus@meduniwien.ac.at.
    Abstract

    INTRODUCTION: The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM.

    METHODS: Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables.

    RESULTS: Plasma activin A level was significantly elevated in MPM patients (862 ± 83 pg/ml) when compared to healthy controls (391 ± 21 pg/ml; P < 0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 625 ± 95 pg/ml; P = 0.0067). Sarcomatoid (n = 10, 1629 ± 202 pg/ml, P = 0.0019) and biphasic (n = 23, 1164 ± 233 pg/ml, P = 0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n = 94, 712 ± 75 pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365 d, P < 0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM.

    CONCLUSIONS: Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.


    Copyright © 2016 Elsevier Ltd. All rights reserved.

    KEYWORDS: Activin A, Biomarker, Malignant pleural mesothelioma, Prognosis

    Publikations ID: 27288871
    Quelle: öffnen
     
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