Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis

Kirschner, Michaela B. and Pulford, Emily and Hoda, Mir Alireza and Rozsas, Anita and Griggs, Kim and Cheng, Yuen Yee and Edelman, J. James B. and Kao, Steven C. and Hyland, Rebecca and Dong, Yawen and László, Viktoria and Klikovits, Thomas and Vallely, Michael P. and Grusch, Michael and Hegedus, Balazs and Dome, Balazs and Klepetko, Walter and van Zandwijk, Nico and Klebe, Sonja and Reid, Glen (2015) Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis. British journal of cancer, 113 (6). pp. 963-9. ISSN 1532-1827

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Abstract

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.

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