Mir Alireza Hoda1, Yawen Dong2, Anita Rozsas3, Thomas Klikovits2, Viktoria Laszlo2, Bahil Ghanim2, Paul Stockhammer2, Judit Ozsvar2, Marko Jakopovic4, Miroslav Samarzija4, Luka Brcic5, Matyas Bendek6, Ildiko Szirtes7, Glen Reid8, Michaela B Kirschner8, Steven C Kao8, Isabelle Opitz9, Walter Weder9, Thomas Frauenfelder10, Thi Dan Linh Nguyen-Kim10, Clemens Aigner11, Walter Klepetko2, Nico van Zandwijk8, Walter Berger12, Balazs Dome13, Michael Grusch12, Balazs Hegedus14. 1. Division 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. 2. Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. 3. Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary. 4. University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia. 5. Medical University of Graz, Institute of Pathology, Graz, Austria. 6. National Koranyi Institute of Pulmonology, Budapest, Hungary. 7. 2nd Institute of Pathology Semmelweis University, Budapest, Hungary. 8. Asbestos Diseases Research Institute, Sydney, Australia. 9. University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland. 10. University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland. 11. Department of Thoracic Surgery, Ruhrlandklinik, Essen, Germany. 12. Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria. 13. Division 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. 14. Division 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.
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.
Authors: Thomas Klikovits; Paul Stockhammer; Viktoria Laszlo; Yawen Dong; Mir Alireza Hoda; Bahil Ghanim; Isabelle Opitz; Thomas Frauenfelder; Thi Dan Linh Nguyen-Kim; Walter Weder; Walter Berger; Michael Grusch; Clemens Aigner; Walter Klepetko; Balazs Dome; Ferenc Renyi-Vamos; Rudolf Oehler; Balazs Hegedus Journal: Sci Rep Date: 2017-11-28 Impact factor: 4.379
Authors: Xiaoling Zhong; Marianne Pons; Christophe Poirier; Yanlin Jiang; Jianguo Liu; George E Sandusky; Safi Shahda; Attila Nakeeb; C Max Schmidt; Michael G House; Eugene P Ceppa; Nicholas J Zyromski; Yunlong Liu; Guanglong Jiang; Marion E Couch; Leonidas G Koniaris; Teresa A Zimmers Journal: J Cachexia Sarcopenia Muscle Date: 2019-07-08 Impact factor: 12.910