Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation

Tumour Biol. 2016 Jan;37(1):1121-9. doi: 10.1007/s13277-015-3913-1. Epub 2015 Aug 15.

Abstract

Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p < 0.001), primary tumor stage (p = 0.017), and distant metastasis (p = 0.017). Low expression of ECRG4 was an independent prognostic indicator for survival of renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

Keywords: DNA methylation; ECRG4; Immunohistochemistry; Prognosis; Renal cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • CpG Islands
  • DNA / chemistry
  • DNA Methylation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / metabolism*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Promoter Regions, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Tumor Suppressor Proteins

Substances

  • Biomarkers, Tumor
  • ECRG4 protein, human
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • DNA