A Combined Shotgun and Targeted Mass Spectrometry Strategy for Breast Cancer Biomarker Discovery

Sjöström, Martin and Ossola, Reto and Breslin, Thomas and Rinner, Oliver and Malmström, Lars and Schmidt, Alexander and Aebersold, Ruedi and Malmström, Johan and Niméus, Emma. (2015) A Combined Shotgun and Targeted Mass Spectrometry Strategy for Breast Cancer Biomarker Discovery. Journal of Proteome Research, 14 (7). pp. 2807-2818.

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Official URL: http://edoc.unibas.ch/40158/

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It is of highest importance to find proteins responsible for breast cancer dissemination, for use as biomarkers or treatment targets. We established and performed a combined nontargeted LC-MS/MS and a targeted LC-SRM workflow for discovery and validation of protein biomarkers. Eighty breast tumors, stratified for estrogen receptor status and development of distant recurrence (DR ± ), were collected. After enrichment of N-glycosylated peptides, label-free LC-MS/MS was performed on each individual tumor in triplicate. In total, 1515 glycopeptides from 778 proteins were identified and used to create a map of the breast cancer N-glycosylated proteome. Based on this specific proteome map, we constructed a 92-plex targeted label-free LC-SRM panel. These proteins were quantified across samples by LC-SRM, resulting in 10 proteins consistently differentially regulated between DR+/DR- tumors. Five proteins were further validated in a separate cohort as prognostic biomarkers at the gene expression level. We also compared the LC-SRM results to clinically reported HER2 status, demonstrating its clinical accuracy. In conclusion, we demonstrate a combined mass spectrometry strategy, at large scale on clinical samples, leading to the identification and validation of five proteins as potential biomarkers for breast cancer recurrence. All MS data are available via ProteomeXchange and PASSEL with identifiers PXD001685 and PASS00643.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Jun 2016 11:00
Deposited On:08 Jun 2016 08:50

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