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

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2017

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Title:: Increased PDGFR-beta and VEGFR-2 protein levels are associated with resistance to platinum-based chemotherapy and adverse outcome of ovarian cancer patients.
Document type:: Journal Article
Author(s):: 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.
Journal title abbreviation:: Oncotarget
Year:: 2017
Journal volume:: 8
Journal issue:: 58
Pages contribution:: 97851-97861
Language:: eng
Fulltext / DOI:: doi:10.18632/oncotarget.18415
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/29228656
TUM Institution:: Frauenklinik und Poliklinik; Institut für Allgemeine Pathologie und Pathologische Anatomie; Institut für Medizinische Statistik und Epidemiologie
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mediaTUM Gesamtbestand Hochschulbibliographie 2017 Fakultäten Medizin Institut für Medizinische Statistik und Epidemiologie

mediaTUM Gesamtbestand Hochschulbibliographie 2017 Fakultäten Medizin Institut für Allgemeine Pathologie und Pathologische Anatomie

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Frauenheilkunde (Prof. Kiechle)2017

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Preclinical Medicine Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.)2017

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Institut für KI und Informatik in der Medizin (Prof. Rückert)2017