title: Coupling proteomics and transcriptomics in the quest of subtype-specific proteins in breast cancer.
abstract: Breast-cancer subtypes present with distinct clinical characteristics. Therefore, characterization of subtype-specific proteins may augment the development of targeted therapies and prognostic biomarkers. To address this issue, MS-based secretome analysis of eight breast cancer cell lines, corresponding to the three main breast cancer subtypes was performed. More than 5200 non-redundant proteins were identified with 23, four, and four proteins identified uniquely in basal, HER2-neu-amplified, and luminal breast cancer cells, respectively. An in silico mRNA analysis using publicly available breast cancer tissue microarray data was carried out as a preliminary verification step. In particular, the expression profiles of 15 out of 28 proteins included in the microarray (from a total of 31 in our subtype-specific signature) showed significant correlation with estrogen receptor (ER) expression. A MS-based analysis of breast cancer tissues was undertaken to verify the results at the proteome level. Eighteen out of 31 proteins were quantified in the proteomes of ER-positive and ER-negative breast cancer tissues. Survival analysis using microarray data was performed to examine the prognostic potential of these selected candidates. Three proteins correlated with ER status at both mRNA and protein levels: ABAT, PDZK1, and PTX3, with the former showing significant prognostic potential.
authors: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors: Maria P
authors: MP
authors: Pavlou
authors: Apostolos
authors: A
authors: Dimitromanolakis
authors: Eleftherios P
authors: EP
authors: Diamandis
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003198:Computer Simulation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C506487:ESR1 protein, human; C484659:PDZK1 protein, human