Browsing by Author "Stahel, Rolf"

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    Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring
    (2013) Cerciello, Ferdinando; Choi, Meena; Nicastri, Annalisa; Bausch-Fluck, Damaris; Ziegler, Annemarie; Vitek, Olga; Felley-Bosco, Emanuela; Stahel, Rolf; Aebersold, Ruedi; Wollscheid, Bernd
    Background: Serum biomarkers can improve diagnosis and treatment of malignant pleural mesothelioma (MPM).However, the evaluation of potential new serum biomarker candidates is hampered by a lack of assay technologies for their clinical evaluation. Here we followed a hypothesis-driven targeted proteomics strategy for the identification and clinical evaluation of MPM candidate biomarkers in serum of patient cohorts. Results: Based on the hypothesis that cell surface exposed glycoproteins are prone to be released from tumor-cells to the circulatory system, we screened the surfaceome of model cell lines for potential MPM candidate biomarkers. Selected Reaction Monitoring (SRM) assay technology allowed for the direct evaluation of the newly identified candidates in serum. Our evaluation of 51 candidate biomarkers in the context of a training and an independent validation set revealed a reproducible glycopeptide signature of MPM in serum which complemented the MPM biomarker mesothelin. Conclusions: Our study shows that SRM assay technology enables the direct clinical evaluation of protein-derived candidate biomarker panels for which clinically reliable ELISA’s currently do not exist.
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    Proteomic surfaceome analysis of mesothelioma
    (2012) Ziegler, Annemarie; Cerciello, Ferdinando; Bigosch, Colette; Bausch-Fluck, Damaris; Felley-Bosco, Emanuela; Ossola, Reto; Soltermann, Alex; Stahel, Rolf; Wollscheid, Bernd
    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 Nglycoproteins, 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 proteinmarker 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.Ina secondary screenoffifteenMPMandsixADCA, weusedhighthroughput 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. Thy1/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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