Header

UZH-Logo

Maintenance Infos

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


Kao, Steven C; Kirschner, Michaela B; Cooper, Wendy A; Tran, Thang; Burgers, Sjaak; Wright, Casey; Korse, Tiny; van den Broek, Daan; Edelman, James; Vallely, Michael; McCaughan, Brian; Pavlakis, Nick; Clarke, Stephen; Molloy, Mark P; van Zandwijk, Nico; Reid, Glen (2016). A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma. British Journal of Cancer, 114(5):524-531.

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.

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.

Statistics

Citations

2 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

5 downloads since deposited on 14 Feb 2017
5 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 March 2016
Deposited On:14 Feb 2017 11:49
Last Modified:21 Nov 2017 19:24
Publisher:Nature Publishing Group
ISSN:0007-0920
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/bjc.2015.470
PubMed ID:26889976

Download

Download PDF  'A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma'.
Preview
Content: Published Version
Filetype: PDF
Size: 968kB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)