Overexpression of astrocyte-elevated gene-1 is associated with ovarian cancer development and progression

Mol Med Rep. 2015 Apr;11(4):2981-90. doi: 10.3892/mmr.2014.3056. Epub 2014 Dec 5.

Abstract

It has previously been reported that astrocyte‑elevated gene‑1 (AEG‑1) has a critical role in the regulation of tumor development, and/or progression. However, the functional significance of AEG‑1 in human ovarian cancer remains unclear. The present study conducted an immunohistochemical analysis of ovarian tissues, and the association between AEG‑1 protein expression, clinicopathological features and outcomes were investigated. The gain or loss of AEG‑1 function was also examined, through exogenous overexpression or knockdown of expression by small interfering RNA, in ovarian cancer cells. Normal ovarian tissue exhibited very little or no AEG‑1 immunoreactivity, whereas high expression levels of AEG‑1 were detected in 12.7% of cystadenomas, 30.0% of borderline tumors, and 71.2% of ovarian carcinomas, respectively, as determined by immunohistochemistry. Statistical analyses demonstrated a significant correlation of AEG‑1 expression with differentiation (P=0.001), lymph node metastasis (P=0.008) and clinical staging (P=0.002). In addition, the overall survival time of patients with higher AEG‑1 expression levels was markedly shorter, as compared with patients with lower expression levels of AEG‑1 (P=0.001). Multivariate analysis indicated that AEG‑1 expression was an independent prognostic indicator of the survival of patients with ovarian cancer. Furthermore, exogenous overexpression of AEG‑1 in ovarian cancer cells was shown to significantly enhance cell proliferation, adhesion and invasion. Conversely, silencing AEG‑1 expression caused an inhibition of cell growth, adhesion and invasion. The results of the present study indicate that AEG‑1 is a valuable biomarker for the prediction of ovarian cancer prognosis, and AEG‑1 inhibition may be a potential therapeutic strategy for ovarian cancer treatment.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Cell Adhesion
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Disease Progression
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Ovary / metabolism
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins