Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma

Pathol Oncol Res. 2020 Jul;26(3):1787-1795. doi: 10.1007/s12253-019-00755-5. Epub 2019 Nov 1.

Abstract

Caveolin-1, the major protein component of caveolae, plays vital functions in tumorigenesis and metastasis. Previous evidence demonstrated the positive role of Caveolin-1 in the regulation of endothelial cell differentiation and the involvement of Caveolin-1 in vascular endothelial growth factor (VEGF) mediated angiogenesis. The correlation of Caveolin-1 expression and angiogenesis is not yet elucidated in osteosarcoma. This study aimed to investigate the expression levels of Caveolin-1 and VEGF in osteosarcoma and their associations with clinicopathological data. This study included 66 formalin-fixed and paraffin embedded osteosarcoma tissue samples. The expression levels of Caveolin-1 and VEGF were assessed by immunohistochemistry. Then associations with clinicopathological variables and the correlation between both markers were evaluated statistically. We also investigated the expression of Caveolin-1 and VEGF values in gene microarrays of osteosarcoma patients and cell lines by using GEO data sets on https://www.ncbi.nlm.nih.gov. Caveolin-1 and VEGF were expressed in 19.6% and 77.3%, respectively. Caveolin-1 expression was associated positively with osteoblastic histological subtype (P < 0.0001). VEGF expression showed positive association with patient age, histological grade and clinical stage (P = 0.031, P = 0.024 and P < 0.001; respectively). An inverse correlation between Caveolin-1 and VEGF expressions in osteosarcoma was found (r = 0.2 P = 0.04). In silico analysis of Caveolin-1 and VEGF expression supported our results. Our results suggest that Caveolin-1 may act as a tumor suppressor in osteosarcoma. Down-regulation of Caveolin-1 can be used as an indicator for poor prognosis in osteosarcoma patients. Meanwhile, overexpression of VEGF is a predictor of pulmonary metastasis and poor prognosis.

Keywords: Caveolin-1; Immunohistochemistry; Osteosarcoma; Vascular endothelial growth factor.

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Caveolin 1 / biosynthesis*
  • Child
  • Female
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Male
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Osteosarcoma / metabolism
  • Osteosarcoma / secondary*
  • Prognosis
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Biomarkers, Tumor
  • CAV1 protein, human
  • Caveolin 1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A