Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma.

Background. Six cell surface receptors, human epidermal growth factor receptor-2 (Her-2), platelet-derived growth factor receptor-β (PDGFR-β), insulin-like growth factor-1 receptor (IGF-1R), insulin receptor (IR), c-Met, and vascular endothelial growth factor receptor-3 (VEGFR-3), previously demonst...

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Publicado en:Sarcoma pp. 1 - 11
Autores principales: Zvi, Yoav, Ugur, Elif, Batko, Brian, Gill, Jonathan, Roth, Michael, Gorlick, Richard, Hall, David, Tingling, Janet, Barkauskas, Donald A., Zhang, Jinghang, Yang, Rui, Hoang, Bang H., Geller, David S.
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 2/2/2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2/2/2021
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2021/8324348
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        atl: Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma.
      aug:
        au:
          Zvi, Yoav
          Ugur, Elif
          Batko, Brian
          Gill, Jonathan
          Roth, Michael
          Gorlick, Richard
          Hall, David
          Tingling, Janet
          Barkauskas, Donald A.
          Zhang, Jinghang
          Yang, Rui
          Hoang, Bang H.
          Geller, David S.
        affil: Department of Orthopaedic Surgery, Montefiore Medical Center, The Children's Hospital at Montefiore, Bronx, NY, USA
      sug:
        subj:
          Osteosarcoma Prognosis
          Receptors, Cell Surface Metabolism
          Osteosarcoma Metabolism
          Human
          Cell Line, Tumor Metabolism
          Antibodies
          Flow Cytometry
          Epidermal Growth Factor Receptors
          Fluorescent Antibody Technique
          Survival Analysis
          Kaplan-Meier Estimator
          Log-Rank Test
          Descriptive Statistics
      ab: Background. Six cell surface receptors, human epidermal growth factor receptor-2 (Her-2), platelet-derived growth factor receptor-β (PDGFR-β), insulin-like growth factor-1 receptor (IGF-1R), insulin receptor (IR), c-Met, and vascular endothelial growth factor receptor-3 (VEGFR-3), previously demonstrated variable expression across varying patient-derived and standard osteosarcoma (OS) cell lines. The current study sought to validate previous expression patterns and evaluate whether these receptors offer prognostic and/or therapeutic value. Methods. Patient-derived OS cell lines (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 difference in geometric mean fluorescent intensity (geoMFIdiff = geoMFIpositive − geoMFInegative) was calculated for each receptor across all cell lines. Receptor expression was categorized as low (Q1), intermediate (Q2, Q3), or high (Q4). The event-free survival (EFS) and overall survival for the six cell surface receptors were estimated by the Kaplan–Meier method. Differences in hazard for EFS event and overall survival event for patients in each of the three expression levels in each of the six cell surface receptors were assessed using the log-rank test. Results. All 6 receptors were variably expressed in the majority of cell lines. IR and PDGFR-β expressions were found to be significant predictors for EFS amongst patients with nonmetastatic disease (p = 0.02 and 0.01, respectively). The hazard ratio for EFS was significantly higher between high IR and intermediate IR expression (HR = 2.66, p = 0.02), as well as between high PDGFR-β and intermediate PDGFR-β expression (HR = 5.68, p = 0.002). Her-2, c-Met, IGF-1R, and VEGFR-3 were not found to be significant predictors for either EFS or overall survival. Conclusion. The six cell surface receptors demonstrated variable expression across the majority of patient-derived OS cell lines tested. Limited prognostic value was offered by IR and PDGFR-β expression within nonmetastatic patients. The remaining receptors do not provide clear prognostic utility. Nevertheless, their consistent, albeit variable, surface expression across a large panel of patient-derived OS cell lines maintains their potential use as future therapeutic targets.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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