title: Proteomic surfaceome analysis of mesothelioma.
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.
authors.affiliation: Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Ziegler
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Cerciello
authors.forename: Colette
authors.initials: C
authors.lastname: Bigosch
authors.forename: Damaris
authors.initials: D
authors.lastname: Bausch-Fluck
authors.forename: Emanuela
authors.initials: E
authors.lastname: Felley-Bosco
authors.forename: Reto
authors.initials: R
authors.lastname: Ossola
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Stahel
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollscheid
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008654:Mesothelioma / Q000737:chemistry*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D018800:Thy-1 Antigens / Q000032:analysis
chemical_list: D008565:Membrane Proteins; D018800:Thy-1 Antigens