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Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma
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  • Yoav Zvi,
  • Elif Ugur,
  • Brian Batko,
  • Jonathan Gill,
  • Michael Roth,
  • Richard Gorlick,
  • David Hall,
  • Janet Tingling,
  • Donald Barkauskas,
  • Jinghang Zhang,
  • Rui Yang,
  • Bang Hoang,
  • David Geller
Yoav Zvi
Montefiore Medical Center
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Elif Ugur
Yeshiva University Albert Einstein College of Medicine
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Brian Batko
Montefiore Medical Center
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Jonathan Gill
University of Texas MD Anderson Cancer Center Children's Cancer Hospital
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Michael Roth
University of Texas MD Anderson Cancer Center Children's Cancer Hospital
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Richard Gorlick
University of Texas MD Anderson Cancer Center
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David Hall
Children's Oncology Group
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Janet Tingling
Montefiore Medical Center
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Donald Barkauskas
Children’s Oncology Group
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Jinghang Zhang
Yeshiva University Albert Einstein College of Medicine
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Rui Yang
Montefiore Medical Center
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Bang Hoang
Montefiore Medical Center
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David Geller
Montefiore Medical Center
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Abstract

Background: Six cell surface receptors, human epidermal growth factor receptor (Her)-2, platelet-derived growth factor receptor (PDGFR)-β, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR), c-Met, and vascular endothelial growth factor receptor (VEGFR)-3, previously demonstrated variable expression across varying osteosarcoma (OS) cell lines. The current study sought to validate previous expression patterns and evaluate whether these receptors offer prognostic and therapeutic value. Methods: Patient-derived OS samples (n = 52) were labeled with antibodies to Her-2, PDGFR-β, IGF-1R, IR, c-Met, and VEGFR-3. Expression was characterized using flow cytometry. The geometric mean fluorescent intensity (geoMFI) for each receptor was calculated relative to a negative control. The event-free survival (EFS) and overall survival for patients with positive receptor expression were estimated by the Kaplan-Meier method. Differences in hazard for EFS event and overall survival event for patients with positive receptor expression were assessed using the log-rank test. Results: All 6 receptors were variably expressed in the majority of cell lines. None of the 6 receptors, were found to be significant predictors of EFS or overall survival. The sum total number of positive receptors per cell line also failed to predict EFS or overall survival. Conclusion: The six cell surface receptors demonstrated variable expression across the majority of patient-derived OS samples tested. While receptor expression did not provide prognostic value, their consistent expression makes them attractive targets for future therapeutic approaches.