TY - JOUR
T1 - Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis
AU - Kirschner, Michaela
AU - Pulford, Emily
AU - Hoda, Mir
AU - Rozsas, Anita
AU - Griggs, Kim
AU - Cheng, Yuen
AU - Edelman, J James
AU - Kao, Steven
AU - Hyland, Rebecca
AU - Dong, Yawen
AU - Laszlo, Victoria
AU - Klikovits, Thomas
AU - Vallely, Michael
AU - Grusch, Michael
AU - Hegedus, Balazs
AU - Dome, Balazs
AU - Klepetko, Walter
AU - van Zandwijk, Nico
AU - Klebe, Sonja
AU - Reid, Glen
PY - 2015/9/15
Y1 - 2015/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941881227&partnerID=8YFLogxK
U2 - 10.1038/bjc.2015.286
DO - 10.1038/bjc.2015.286
M3 - Article
SN - 0007-0920
VL - 113
SP - 963
EP - 969
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 6
ER -
