A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma

Steven C. Kao*, Michaela B. Kirschner, Wendy A. Cooper, Thang Tran, Sjaak Burgers, Casey Wright, Tiny Korse, Daan Van Den Broek, James Edelman, Michael Vallely, Brian Mccaughan, Nick Pavlakis, Stephen Clarke, Mark P. Molloy, Nico Van Zandwijk, Glen Reid

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Background:We aimed to identify prognostic blood biomarkers using proteomics-based approaches in malignant pleural mesothelioma (MPM).Methods:Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n=97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts.Results:Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P=0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P=0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC.Conclusions:Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC.

Original languageEnglish
Pages (from-to)524-531
Number of pages8
JournalBritish Journal of Cancer
Volume114
Issue number5
DOIs
Publication statusPublished - 1 Mar 2016

Keywords

  • ELISA
  • malignant pleural mesothelioma
  • prognosis
  • proteomics
  • SPARC

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