Journal
JOURNAL OF PROTEOME RESEARCH
Volume 13, Issue 11, Pages 4730-4738Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr500253j
Keywords
tumor-associated stroma; breast cancer; MALDI imaging mass spectrometry; MSI; multicenter study; proteomics
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Funding
- Cyttron II project Imaging Mass Spectrometry
- COMMIT project e-biobanking
- ZonMw Zenith project 'Imaging Mass Spectrometry-Based Molecular Histology: Differentiation and Characterization of Clinically Challenging Soft Tissue Sarcomas'
- COST Action [BM1104]
- Marie Curie Intra European Fellowship [331866]
- Ministry of Education and Research of the Federal Republic of Germany (BMBF) [0315505A, 01IB10004E]
- Deutsche Forschungsgemeinschaft [SFB 824 TP Z02, WA 1656/3-1]
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MALDI mass spectrometry imaging (MSI) has rapidly established itself as a powerful biomarker discovery tool. To date, no formal investigation has assessed the center-to-center comparability of MALDI MSI experiments, an essential step for it to develop into a new diagnostic method. To test such capabilities, we have performed a multicenter study focused on biomarkers of stromal activation in breast cancer. MALDI MSI experiments were performed in two centers using independent tissue banks, infrastructure, methods, and practitioners. One of the data sets was used for discovery and the other for validation. Areas of intra- and extratumoral stroma were selected, and their protein signals were compared. Four protein signals were found to be significantly associated with tumor-associated stroma in the discovery data set measured in Munich. Three of these peaks were also detected in the independent validation data set measured in Leiden, all of which were also significantly associated with intratumoral stroma. Hierarchical clustering displayed 100% accuracy in the Munich MSI data set and 80.9% accuracy in the Leiden MSI data set. The association of one of the identified mass signals (PA28) with stromal activation was confirmed with immunohistochemistry performed on 20 breast tumors. Independent and international MALDI MSI investigations could identify validated biomarkers of stromal activation.
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