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Proteomic surfaceome analysis of mesothelioma


Ziegler, A; Cerciello, F; Bigosch, C; Bausch-Fluck, D; Felley-Bosco, E; Ossola, R; Soltermann, A; Stahel, R A; Wollscheid, B (2012). Proteomic surfaceome analysis of mesothelioma. Lung Cancer, 75(2):189-196.

Abstract

Identification of new markers for malignant pleural mesothelioma (MPM) is a challenging clinical need. Here, we propose a quantitative proteomics primary screen of the cell surface exposed MPM N-glycoproteins, which provides the basis for the development of new protein-based diagnostic assays. Using the antibody-independent mass-spectrometry based cell surface capturing (CSC) technology, we specifically investigated the N-glycosylated surfaceome of MPM towards the identification of protein-marker candidates discriminatory between MPM and lung adenocarcinoma (ADCA). Relative quantitative CSC analysis of MPM cell line ZL55 in comparison with ADCA cell line Calu-3 revealed a bird's eye view of their respective surfaceomes. In a secondary screen of fifteen MPM and six ADCA, we used high throughput low density microarrays (LDAs) to verify specificity and sensitivity of nineteen N-glycoproteins overregulated in the surfaceome of MPM. This proteo-transcriptomic approach revealed thy-1/CD90 (THY1) and teneurin-2 (ODZ2) as protein-marker candidates for the discrimination of MPM from ADCA. Thy-1/CD90 was further validated by immunohistochemistry on frozen tissue sections of MPM and ADCA samples. Together, we present a combined proteomic and transcriptomic approach enabling the relative quantitative identification and pre-clinical selection of new MPM marker candidates.

Identification of new markers for malignant pleural mesothelioma (MPM) is a challenging clinical need. Here, we propose a quantitative proteomics primary screen of the cell surface exposed MPM N-glycoproteins, which provides the basis for the development of new protein-based diagnostic assays. Using the antibody-independent mass-spectrometry based cell surface capturing (CSC) technology, we specifically investigated the N-glycosylated surfaceome of MPM towards the identification of protein-marker candidates discriminatory between MPM and lung adenocarcinoma (ADCA). Relative quantitative CSC analysis of MPM cell line ZL55 in comparison with ADCA cell line Calu-3 revealed a bird's eye view of their respective surfaceomes. In a secondary screen of fifteen MPM and six ADCA, we used high throughput low density microarrays (LDAs) to verify specificity and sensitivity of nineteen N-glycoproteins overregulated in the surfaceome of MPM. This proteo-transcriptomic approach revealed thy-1/CD90 (THY1) and teneurin-2 (ODZ2) as protein-marker candidates for the discrimination of MPM from ADCA. Thy-1/CD90 was further validated by immunohistochemistry on frozen tissue sections of MPM and ADCA samples. Together, we present a combined proteomic and transcriptomic approach enabling the relative quantitative identification and pre-clinical selection of new MPM marker candidates.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:15 Dec 2011 08:43
Last Modified:05 Apr 2016 15:15
Publisher:Elsevier
ISSN:0169-5002
Publisher DOI:10.1016/j.lungcan.2011.07.009
PubMed ID:21835491
Permanent URL: http://doi.org/10.5167/uzh-53099

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