title: CCNJ detected by triple combination array analysis as a tumor-related gene of hepatocellular carcinoma.
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.
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Nao
authors: N
authors: Takano
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Mitsuhiro
authors: M
authors: Hishida
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Yoshikuni
authors: Y
authors: Inokawa
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Masamichi
authors: M
authors: Hayashi
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Mitsuro
authors: M
authors: Kanda
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Yoko
authors: Y
authors: Nishikawa
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Naoki
authors: N
authors: Iwata
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Daisuke
authors: D
authors: Kobayashi
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Chie
authors: C
authors: Tanaka
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Suguru
authors: S
authors: Yamada
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Goro
authors: G
authors: Nakayama
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Tsutomu
authors: T
authors: Fujii
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Hiroyuki
authors: H
authors: Sugimoto
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Masahiko
authors: M
authors: Koike
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Michitaka
authors: M
authors: Fujiwara
authors: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors: Yasuhiro
authors: Y
authors: Kodera
authors: Department of Surgery, Aichi-Gakuin University School of Dentistry, Chikusa-ku, Nagoya 464-8651, Japan.
authors: Shuji
authors: S
authors: Nomoto
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics*; D016213:Cyclins / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D046888:Tissue Array Analysis / Q000379:methods*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C000589891:CCNJ protein, human; D016213:Cyclins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins