Identification of Stage-Specific Breast Markers using Quantitative Proteomics
View/ Open
shaheed_et_al_2013.pdf (1.174Mb)
Download
Publication date
2013Author
Shaheed, Sadr-ulRustogi, Nitin
Scally, Andy J.
Wilson, J.
Thygesen, H.
Loizidou, M.A.
Hadjisavvas, A.
Hanby, A.
Speirs, V.
Loadman, Paul
Linforth, R.
Kyriacou, K.
Sutton, Chris W.
Keyword
Breast cancerInvasive carcinoma
DCIS
Fibroadenoma
Proteomics
iTRAQ
Mass spectrometry
Tissue microarray
Western blotting
Rights
� 2013 American Chemical Society. Full-text reproduced in accordance with the publisher's self-archiving policy.Peer-Reviewed
YesOpen Access status
openAccessopenAccess
Metadata
Show full item recordAbstract
Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Version
Accepted manuscriptCitation
Shaheed S, Rustogi N, Scally AJ et al (2013) Identification of Stage-Specific Breast Markers Using Quantitative Proteomics. Journal of Proteome Research. 12(12): 5696-5708.Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1021/pr400662k