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

Takano,Nao; Hishida,Mitsuhiro; Inokawa,Yoshikuni; Hayashi,Masamichi; Kanda,Mitsuro; Nishikawa,Yoko; Iwata,Naoki; Kobayashi,Daisuke; Tanaka,Chie; Yamada,Suguru; Nakayama,Goro; Fujii,Tsutomu; Sugimoto,Hiroyuki; Koike,Masahiko; Fujiwara,Michitaka; Kodera,Yasuhiro; Nomoto,Shuji

doi:10.3892/ijo.2015.2892

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

Authors:
- Nao Takano
- Mitsuhiro Hishida
- Yoshikuni Inokawa
- Masamichi Hayashi
- Mitsuro Kanda
- Yoko Nishikawa
- Naoki Iwata
- Daisuke Kobayashi
- Chie Tanaka
- Suguru Yamada
- Goro Nakayama
- Tsutomu Fujii
- Hiroyuki Sugimoto
- Masahiko Koike
- Michitaka Fujiwara
- Yasuhiro Kodera
- Shuji Nomoto
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Affiliations: Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan, Department of Surgery, Aichi-Gakuin University School of Dentistry, Chikusa-ku, Nagoya 464-8651, Japan
Published online on: February 11, 2015 https://doi.org/10.3892/ijo.2015.2892
Pages: 1963-1970

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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.

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