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

Autor: Thang N Tran, Glen Reid, Nico van Zandwijk, Michael P. Vallely, Stephen Clarke, T. Korse, Nick Pavlakis, Michaela B. Kirschner, Mark P. Molloy, Sjaak Burgers, Daan van den Broek, J. James B. Edelman, Brian C. McCaughan, Wendy A Cooper, Casey M. Wright, Steven Kao
Přispěvatelé: University of Zurich, Kao, Steven C
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Mesothelioma
Proteomics
Cancer Research
Pathology
Lung Neoplasms
10255 Clinic for Thoracic Surgery
Mass Spectrometry
Mice
0302 clinical medicine
Medicine
1306 Cancer Research
Osteonectin
biology
Middle Aged
Prognosis
Immunohistochemistry
Survival Rate
Oncology
030220 oncology & carcinogenesis
2730 Oncology
ELISA
Female
medicine.medical_specialty
Pleural Neoplasms
610 Medicine & health
Enzyme-Linked Immunosorbent Assay
03 medical and health sciences
In vivo
Cell Line
Tumor
Biomarkers
Tumor
malignant pleural mesothelioma
Animals
Humans
Secretion
Molecular Diagnostics
Proportional Hazards Models
Retrospective Studies
business.industry
Mesothelioma
Malignant
SPARC
medicine.disease
In vitro
030104 developmental biology
Cell culture
Tissue Array Analysis
Multivariate Analysis
biology.protein
Cancer research
business
Neoplasm Transplantation
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: 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.
Databáze: OpenAIRE
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