期刊
CLINICAL PROTEOMICS
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1559-0275-10-16
关键词
Malignant pleural mesothelioma; Selected reaction monitoring; Surfaceome; Targeted proteomics; Serum biomarkers
资金
- Swiss national MD-PhD program of the Swiss National Science Foundation (SNSF)
- Cancer Biology program of the University of Zurich
- Cancer League of Zurich
- Huggenberger-Bischoff foundation for Cancer Research
- NCCR Neural Plasticity and Repair of the SNSF
- BIP SystemsX.ch
- SNSF [3100A0-107679]
- European Research Council [ERC-2008-AdG 233226]
- grant Prime-X (EC)
- Laboratory of Molecular Oncology
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1054826] Funding Source: National Science Foundation
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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