A mass spectrometry-based plasma protein panel targeting the tumor microenvironment in patients with breast cancer

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DOIResolve DOI: http://doi.org/10.1016/j.jprot.2012.11.004
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TypeArticle
Journal titleJournal of Proteomics
ISSN1874-3919
Volume81
Pages135147; # of pages: 13
Subjectbreast cancer; tumor microenvironment; plasma proteomics; intraprotein variability
AbstractProteins secreted or shed by cancerous cells are seen as a rich source of biomarkers and novel therapeutic targets. Recently, the importance of the tumor microenvironment, which comprises the surrounding non-tumor cells, has received increased attention for its role in tumor progression. We developed a targeted proteomics assay to monitor a panel of plasma proteins postulated to be present in the tumor microenvironment. The plasma of 76 breast cancer patients was depleted of abundant circulating proteins, enzymatically digested and labeled by reductive methylation. The labeled digests were analyzed by tandem mass spectrometry using a multiple reaction monitoring acquisition method. The protein targets were correlated with the tumor characteristics, the extent of the disease and the clinical staging of the patients. Linear discriminant analysis revealed that infiltrating ductal and invasive mammary breast carcinomas could be grouped based on distinctive peptide levels of fibronectin, clusterin, gelsolin and α-1-microglobulin/Inter-α-trypsin inhibitor light chain precursor (AMBP). These proteins have been previously associated with breast cancer at the tissue level, however, this is the first study to measure plasma levels of these proteins and correlate these levels with clinical features. Significant variability was seen between unique peptides belonging to the same protein. This article is part of a Special Issue entitled: From protein structures to clinical applications.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NRC number53184
NPARC number21268242
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Record identifier923e0e9f-3606-4c8c-9f89-77368d4c69c2
Record created2013-06-07
Record modified2016-05-09
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