Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis.
BACKGROUND
Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies.


METHODS
ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively.


RESULTS
FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)).


CONCLUSIONS
These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients.
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.|Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
Michaela B
MB
Kirschner
Department of Anatomical Pathology, Flinders University and SA Pathology, Adelaide, SA 5042, Australia.
Emily
E
Pulford
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Mir Alireza
MA
Hoda
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Anita
A
Rozsas
Department of Anatomical Pathology, Flinders University and SA Pathology, Adelaide, SA 5042, Australia.
Kim
K
Griggs
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.
Yuen Yee
YY
Cheng
Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital; The Baird Institute; The University of Sydney, Sydney, NSW 2050, Australia.
J James B
JJ
Edelman
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW 2050, Australia.
Steven C
SC
Kao
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.
Rebecca
R
Hyland
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Yawen
Y
Dong
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Viktoria
V
László
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Thomas
T
Klikovits
Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.|Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital; The Baird Institute; The University of Sydney, Sydney, NSW 2050, Australia.|Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia.
Michael P
MP
Vallely
Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria.
Michael
M
Grusch
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.|MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, 1051 Budapest, Hungary.
Balazs
B
Hegedus
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.|Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, 1090 Vienna, Austria.|Department of Thoracic Surgery, National Institute of Oncology, 1122 Budapest, Hungary.|Department of Tumor Biology, National Koranyi Institute of Pulmonology and Semmelweis University, 1085 Budapest, Hungary.
Balazs
B
Dome
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria.
Walter
W
Klepetko
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.|Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
Nico
N
van Zandwijk
Department of Anatomical Pathology, Flinders University and SA Pathology, Adelaide, SA 5042, Australia.
Sonja
S
Klebe
Asbestos Diseases Research Institute (ADRI), Sydney, NSW 2139, Australia.|Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
Glen
G
Reid
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010996:Pleural Effusion / Q000378:metabolism; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011379:Prognosis
D014408:Biomarkers, Tumor; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins