Heyde, Silvia von der

[["dc.bibliographiccitation.firstpage","52"],["dc.bibliographiccitation.journal","Translational Proteomics"],["dc.bibliographiccitation.lastpage","59"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Sonntag, Johanna"],["dc.contributor.author","Bender, Christian"],["dc.contributor.author","Soons, Zita"],["dc.contributor.author","Heyde, Silvia von der"],["dc.contributor.author","König, Rainer"],["dc.contributor.author","Wiemann, Stefan"],["dc.contributor.author","Sinn, Hans-Peter"],["dc.contributor.author","Schneeweiss, Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Korf, Ulrike"],["dc.date.accessioned","2019-07-09T11:40:49Z"],["dc.date.available","2019-07-09T11:40:49Z"],["dc.date.issued","2014"],["dc.description.abstract","A robust subclassification of luminal breast cancer, the most common molecular subtype of human breast cancer, is crucial for therapy decisions. While a part of patients is at higher risk of recurrence and requires chemo-endocrine treatment, the other part is at lower risk and also poorly responds to chemotherapeutic regimens. To approximate the risk of cancer recurrence, clinical guidelines recommend determining histologic grading and abundance of a cell proliferation marker in tumor specimens. However, this approach assigns an intermediate risk to a substantial number of patients and in addition suffers from a high interobserver variability. Therefore, the aim of our study was to identify a quantitative protein biomarker signature to facilitate risk classification. Reverse phase protein arrays (RPPA) were used to obtain quantitative expression data for 128 breast cancer relevant proteins in a set of hormone receptor-positive tumors (n = 109). Proteomic data for the subset of histologic G1 (n = 14) and G3 (n = 22) samples were used for biomarker discovery serving as surrogates of low and high recurrence risk, respectively. A novel biomarker selection workflow based on combining three different classification methods identified caveolin-1, NDKA, RPS6, and Ki-67 as top candidates. NDKA, RPS6, and Ki-67 were expressed at elevated levels in high risk tumors whereas caveolin-1 was observed as downregulated. The identified biomarker signature was subsequently analyzed using an independent test set (AUC = 0.78). Further evaluation of the identified biomarker panel by Western blot and mRNA profiling confirmed the proteomic signature obtained by RPPA. In conclusion, the biomarker signature introduced supports RPPA as a tool for cancer biomarker discovery."],["dc.identifier.doi","10.1016/j.trprot.2014.02.001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11379"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58260"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Reverse phase protein array based tumor profiling identifies a biomarker signature for risk classification of hormone receptor-positive breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","UNSP e16"],["dc.bibliographiccitation.journal","Oncogenesis"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Henjes, Frauke"],["dc.contributor.author","Bender, Christian"],["dc.contributor.author","Heyde, Silvia von der"],["dc.contributor.author","Braun, L."],["dc.contributor.author","Mannsperger, Heiko A."],["dc.contributor.author","Schmidt, C."],["dc.contributor.author","Wiemann, Stefan"],["dc.contributor.author","Hasmann, M."],["dc.contributor.author","Aulmann, S."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Korf, Ulrike"],["dc.date.accessioned","2018-11-07T09:08:57Z"],["dc.date.available","2018-11-07T09:08:57Z"],["dc.date.issued","2012"],["dc.description.abstract","Increasing the efficacy of targeted cancer therapies requires the identification of robust biomarkers suitable for patient stratification. This study focused on the identification of molecular mechanisms causing resistance against the anti-ERBB2-directed therapeutic antibodies trastuzumab and pertuzumab presently used to treat patients with ERBB2-amplified breast cancer. Immunohistochemistry and clinical data were evaluated and yielded evidence for the existence of ERBB2-amplified breast cancer with high-level epidermal growth-factor receptor (EGFR) expression as a separate tumor entity. Because the proto-oncogene EGFR tightly interacts with ERBB2 on the protein level, the hypothesis that high-level EGFR expression might contribute to resistance against ERBB2-directed therapies was experimentally validated. SKBR3 and HCC1954 cells were chosen as model systems of EGFR-high/ERBB2-amplified breast cancer and exposed to trastuzumab, pertuzumab and erlotinib, respectively, and in combination. Drug impact was quantified in cell viability assays and on the proteomic level using reverse-phase protein arrays. Phosphoprotein dynamics revealed a significant downregulation of AKT signaling after exposure to trastuzumab, pertuzumab or a coapplication of both antibodies in SKBR3 cells but no concomitant impact on ERK1/2, RB or RPS6 phosphorylation. On the other hand, signaling was fully downregulated in SKBR3 cells after coinhibition of EGFR and ERBB2. Inhibitory effects in HCC1954 cells were driven by erlotinib alone, and a significant upregulation of RPS6 and RB phosphorylation was observed after coincubation with pertuzumab and trastuzumab. In summary, proteomic data suggest that high-level expression of EGFR in ERBB2-amplified breast cancer cells attenuates the effect of anti-ERBB2-directed antibodies. In conclusion, EGFR expression may serve as diagnostic and predictive biomarker to advance personalized treatment concepts of patients with ERBB2-amplified breast cancer."],["dc.identifier.doi","10.1038/oncsis.2012.16"],["dc.identifier.isi","000209219200001"],["dc.identifier.pmid","23552733"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10849"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26148"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2157-9024"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Strong EGFR signaling in cell line models of ERBB2-amplified breast cancer attenuates response towards ERBB2-targeting drugs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]