Increased PDGFR-beta and VEGFR-2 protein levels are associated with resistance to platinum-based chemotherapy and adverse outcome of ovarian cancer patients.

Avril, Stefanie; Dincer, Yasemin; Malinowsky, Katharina; Wolff, Claudia; Gündisch, Sibylle; Hapfelmeier, Alexander; Boxberg, Melanie; Bronger, Holger; Becker, Karl-Friedrich; Schmalfeldt, Barbara

doi:10.18632/oncotarget.18415

Benutzer: Gast

journal article

Titel:: Increased PDGFR-beta and VEGFR-2 protein levels are associated with resistance to platinum-based chemotherapy and adverse outcome of ovarian cancer patients.
Dokumenttyp:: journal article
Autor(en):: Avril, Stefanie; Dincer, Yasemin; Malinowsky, Katharina; Wolff, Claudia; Gündisch, Sibylle; Hapfelmeier, Alexander; Boxberg, Melanie; Bronger, Holger; Becker, Karl-Friedrich; Schmalfeldt, Barbara
Abstract:: Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response.192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity. Quantitative reverse-phase-protein-arrays were used to analyze protein and phospho-protein levels of 41 signaling molecules including growth-factor receptors, AKT and MAPK signaling pathways as well as angiogenesis and cell-adhesion.Platinum-resistant ovarian cancers (56/192) demonstrated significantly higher intratumoral levels of the angiogenesis-associated growth-factor receptors PDGFR-beta and VEGFR2 compared to platinum-sensitive tumors. In addition, patients with high PDGFR-beta expression had significantly shorter overall and progression-free survival (HR 3.6 and 2.4; p< 0.001). The prognostic value of PDGFR-beta and VEGFR2 was confirmed in publicly available microarray-datasets.High intratumoral levels of the angiogenesis-related growth-factor receptors PDGFR-beta and VEGFR2 might serve as novel predictive biomarkers to identify primary resistance to platinum-based chemotherapy. Those ovarian cancer patients might particularly benefit from additional anti-vascular therapy including anti-VEGF antibody or receptor tyrosine-kinase-inhibitor therapy.
Zeitschriftentitel:: Oncotarget
Jahr:: 2017
Sprache:: eng
Volltext / DOI:: doi:10.18632/oncotarget.18415
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/28622685
TUM Einrichtung:: Institut für Allgemeine Pathologie und pathologische Anatomie
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