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

被引:11
作者
Takano, Nao [1 ]
Hishida, Mitsuhiro [1 ]
Inokawa, Yoshikuni [1 ]
Hayashi, Masamichi [1 ]
Kanda, Mitsuro [1 ]
Nishikawa, Yoko [1 ]
Iwata, Naoki [1 ]
Kobayashi, Daisuke [1 ]
Tanaka, Chie [1 ]
Yamada, Suguru [1 ]
Nakayama, Goro [1 ]
Fujii, Tsutomu [1 ]
Sugimoto, Hiroyuki [1 ]
Koike, Masahiko [1 ]
Fujiwara, Michitaka [1 ]
Kodera, Yasuhiro [1 ]
Nomoto, Shuji [1 ,2 ]
机构
[1] Nagoya Univ, Gastroenterol Surg, Grad Sch Med, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Aichi Gakuin Univ, Dept Surg, Sch Dent, Chikusa Ku, Nagoya, Aichi 4648651, Japan
基金
日本学术振兴会;
关键词
cyclin J; hepatocellular carcinoma; methylation; triple combination array; cancer-related gene; SUPPRESSOR GENE; IDENTIFICATION; EXPRESSION; DNA; CANCER; RISK; G1;
D O I
10.3892/ijo.2015.2892
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 CCAU. 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.
引用
收藏
页码:1963 / 1970
页数:8
相关论文
共 38 条
[1]  
Bates S, 1996, ONCOGENE, V13, P1103
[2]   Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B′ subunits in active complexes and induces nuclear aberrations and a G1/S phase cell cycle arrest [J].
Bennin, DA ;
Don, ASA ;
Brake, T ;
McKenzie, JL ;
Rosenbaum, H ;
Ortiz, L ;
DePaoli-Roach, AA ;
Horne, MC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (30) :27449-27467
[3]   Novel systemic therapy options for hepatocellular carcinoma [J].
Cusnir, M ;
Patt, YZ .
CANCER JOURNAL, 2004, 10 (02) :97-103
[4]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[5]   miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9 [J].
Feliciano, Andrea ;
Castellvi, Josep ;
Artero-Castro, Ana ;
Leal, Jose A. ;
Romagosa, Cleofe ;
Hernandez-Losa, Javier ;
Peg, Vicente ;
Fabra, Angels ;
Vidal, Francisco ;
Kondoh, Hiroshi ;
Ramon y Cajal, Santiago ;
LLeonart, Matilde E. .
PLOS ONE, 2013, 8 (10)
[6]   Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].
Ferlay, Jacques ;
Shin, Hai-Rim ;
Bray, Freddie ;
Forman, David ;
Mathers, Colin ;
Parkin, Donald Maxwell .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917
[7]   Isolation of Drosophila cyclin D, a protein expressed in the morphogenetic furrow before entry into S phase [J].
Finley, RL ;
Thomas, BJ ;
Zipursky, SL ;
Brent, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :3011-3015
[8]   MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells [J].
Fornari, Francesca ;
Gramantieri, Laura ;
Giovannini, Catia ;
Veronese, Angelo ;
Ferracin, Manuela ;
Sabbioni, Silvia ;
Calin, George Adrian ;
Grazi, Gian Luca ;
Croce, Carlo Maria ;
Tavolari, Simona ;
Chieco, Pasquale ;
Negrini, Massimo ;
Bolondi, Luigi .
CANCER RESEARCH, 2009, 69 (14) :5761-5767
[9]   Hepatocellular carcinoma [J].
Forner, Alejandro ;
Llovet, Josep M. ;
Bruix, Jordi .
LANCET, 2012, 379 (9822) :1245-1255
[10]   Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma [J].
Gramantieri, Laura ;
Ferracin, Manuela ;
Fornari, Francesca ;
Veronese, Airtgelo ;
Sabbioni, Silvia ;
Liu, Chang-Gong ;
Calin, George A. ;
Giovannini, Catia ;
Ferrazzi, Eros ;
Grazi, Gian Luca ;
Croce, Carlo M. ;
Bolondi, Luigi ;
Negrini, Massimo .
CANCER RESEARCH, 2007, 67 (13) :6092-6099