Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma - A multi-institutional study.
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.



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.



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.



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.
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.
Mir Alireza
MA
Hoda
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Yawen
Y
Dong
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; National Koranyi Institute of Pulmonology, Budapest, Hungary.
Anita
A
Rozsas
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Thomas
T
Klikovits
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Viktoria
V
Laszlo
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Bahil
B
Ghanim
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Paul
P
Stockhammer
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Judit
J
Ozsvar
University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia.
Marko
M
Jakopovic
University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, Croatia.
Miroslav
M
Samarzija
Medical University of Graz, Institute of Pathology, Graz, Austria.
Luka
L
Brcic
National Koranyi Institute of Pulmonology, Budapest, Hungary.
Matyas
M
Bendek
2nd Institute of Pathology Semmelweis University, Budapest, Hungary.
Ildiko
I
Szirtes
Asbestos Diseases Research Institute, Sydney, Australia.
Glen
G
Reid
Asbestos Diseases Research Institute, Sydney, Australia.
Michaela B
MB
Kirschner
Asbestos Diseases Research Institute, Sydney, Australia.
Steven C
SC
Kao
University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland.
Isabelle
I
Opitz
University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland.
Walter
W
Weder
University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland.
Thomas
T
Frauenfelder
University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich, Switzerland.
Thi Dan Linh
TD
Nguyen-Kim
Department of Thoracic Surgery, Ruhrlandklinik, Essen, Germany.
Clemens
C
Aigner
Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Walter
W
Klepetko
Asbestos Diseases Research Institute, Sydney, Australia.
Nico
N
van Zandwijk
Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Walter
W
Berger
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.
Balazs
B
Dome
Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Michael
M
Grusch
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.
Balazs
B
Hegedus
D028341:Activins / Q000097:blood*; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000097:blood* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000097:blood* / Q000473:pathology; D011379:Prognosis
D014408:Biomarkers, Tumor; C422405:activin A; D028341:Activins; D005340:Fibrinogen
Activin A; Biomarker; Malignant pleural mesothelioma; Prognosis