Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma

Gene. 2017 Sep 20:629:29-34. doi: 10.1016/j.gene.2017.07.077. Epub 2017 Jul 29.

Abstract

The brother of the regulator of the imprinted site (BORIS), an 11 zinc finger (ZF) protein, is a paralogue of CCCTC-binding factor (CTCF), involves in a few crucial events of chromatin functions, complex transcription regulation during spermatogenesis. As a novel tumor oncogene, abnormal expression of BORIS is observed in human hepatocellular carcinoma, however, the underlying mechanisms remain largely unexplored. In this study, the methylation status of BORIS was tested by methylation specific polymerase chain reaction (MSP) in human HCC cell lines and 43 pairs of tissue specimens. Frequently demethylation of BORIS in HCC was significantly higher than that in the paired adjacent non-tumor tissues (P=0.019), and it was correlated with tumor size (P=0.025) and clinical TNM stage (P=0.035). Patients with hypomethylated BORIS had a shorter disease free survival than those without demethylated BORIS (P=0.006). Further, analyses using Cox regression have indicated that the BORIS demethylation status was an independent risk to the reduced overall survival rate of HCC patients (P=0.035). These findings provide clues to clarify whether the demethylation may lead to activation of the promoter for upregulation expression of BORIS. In conclusions, aberrant BORIS hypomethylation is a promising biomarker for the prognosis of HCC.

Keywords: BORIS; DNA demethylation; HCC; MSP; Prognosis.

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • DNA Methylation*
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*

Substances

  • CTCFL protein, human
  • DNA-Binding Proteins