CCNJ detected by triple combination array analysis as a tumor-related gene of hepatocellular carcinoma

Int J Oncol. 2015 May;46(5):1963-70. doi: 10.3892/ijo.2015.2892. Epub 2015 Feb 11.

Abstract

Hepatocellular carcinoma (HCC) has a high likelihood of recurrence and a poor prognosis. To detect cancer-related genes of HCC, we developed a new technique: triple combination array analysis, consisting of a methylation array, a gene expression array and a single nucleotide polymorphism array. A surgical specimen obtained from a 68-year-old female HCC patient was analyzed using triple combination array, which identified cyclin J (CCNJ) as a candidate cancer-related gene of HCC. Subsequently, samples from 85 HCC patients were evaluated for CCNJ promoter hypermethylation and expression status using methylation-specific PCR (MSP) and quantitative reverse transcriptase RT-PCR, respectively. CCNJ was found to be hypermethylated (methylation value, 0.906; range, 0-1.0) in cancer tissue, compared with adjacent non-cancerous tissue (0.112) using a methylation array. MSP revealed that CCNJ was hypermethylated in 67 (78.8%) of the tumor samples. CCNJ expression was significantly decreased in cases with hypermethylation (P<0.0001). Furthermore, cases with both promoter hypermethylation and decreased expression of CCNJ in the tumor tissue had a worse overall survival than the other cases (P=0.0383). In conclusion, our results indicated that CCNJ could be a novel prognostic marker of HCC, and this study indicated that triple combination array analysis was effective in detecting new tumor-related genes and their mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Cyclins / genetics*
  • DNA Methylation / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Male
  • Methylation
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Tissue Array Analysis / methods*
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • CCNJ protein, human
  • Cyclins
  • DNA, Neoplasm
  • Neoplasm Proteins