Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data

被引:49
作者
Kittaka, Nobuyoshi [1 ]
Takemasa, Ichiro [1 ]
Takeda, Yutaka [1 ]
Marubashi, Shigeru [1 ]
Nagano, Hiroaki [1 ]
Umeshita, Koji [1 ]
Dono, Keizo [1 ]
Matsubara, Kenichi [2 ]
Matsuura, Nariaki [3 ]
Monden, Morito [1 ]
机构
[1] Osaka Univ, Dept Surg, Grad Sch Med, Suita, Osaka 5650871, Japan
[2] DNA Chip Res Inc, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
[3] Osaka Univ, Dept Funct Diagnost Sci, Grad Sch Med, Suita, Osaka 5650871, Japan
关键词
DNA microarray; network analysis; integrative method; 'hotspot' region; biological insight;
D O I
10.1016/j.ejca.2008.02.019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
DNA microarray analysis of human cancer has resulted in considerable accumulation of global gene profiles. However, extraction and understanding the underlying biology of cancer progression remains a significant challenge. This study applied a novel integrative computational and analytical approach to this challenge in human hepatocellular carcinoma (HCC) with the aim of identifying potential molecular markers or novel therapeutic targets. We analysed 100 HCC tissue samples by human 30 K DNA microarray. The gene expression data were uploaded into the network analysis tool, and the biological networks were displayed graphically. We identified several activated 'hotspot' regions harbouring a concentration of upregulated genes. Several 'hotspot' regions revealed integrin and Akt/NF-kappa B signalling. We identified key members linked to these signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2 (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should significantly enhance the power of microarray data in identifying novel potential targets in human cancer. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:885 / 897
页数:13
相关论文
共 30 条
[1]   HEPATOBLASTOMA - AN IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL-STUDY [J].
ABENOZA, P ;
MANIVEL, JC ;
WICK, MR ;
HAGEN, K ;
DEHNER, LP .
HUMAN PATHOLOGY, 1987, 18 (10) :1025-1035
[2]   Activation of Wnt/β-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice [J].
Apte, Udayan ;
Zeng, Gang ;
Muller, Peggy ;
Tan, Xinping ;
Micsenyi, Amanda ;
Cieply, Benjamin ;
Dai, Chunsun ;
Liu, Youhua ;
Kaestner, Klaus H. ;
Monga, Satdarshan P. S. .
HEPATOLOGY, 2006, 44 (04) :992-1002
[3]   Genetic dissection of transcriptional regulation in budding yeast [J].
Brem, RB ;
Yvert, G ;
Clinton, R ;
Kruglyak, L .
SCIENCE, 2002, 296 (5568) :752-755
[4]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[5]   Glypican-3: A novel serum and histochemical marker for hepatocellular carcinoma [J].
Capurro, M ;
Wanless, IR ;
Sherman, M ;
Deboer, G ;
Shi, W ;
Miyoshi, E ;
Filmus, J .
GASTROENTEROLOGY, 2003, 125 (01) :89-97
[6]   Annexins: From structure to function [J].
Gerke, V ;
Moss, SE .
PHYSIOLOGICAL REVIEWS, 2002, 82 (02) :331-371
[7]   Metabolomics: Current technologies and future trends [J].
Hollywood, Katherine ;
Brison, Daniel R. ;
Goodacre, Royston .
PROTEOMICS, 2006, 6 (17) :4716-4723
[8]   A BIOCHEMICAL-CHARACTERIZATION OF THE BINDING OF OSTEOPONTIN TO INTEGRINS ALPHA(V)BETA(1) AND ALPHA(V)BETA(5) [J].
HU, DD ;
LIN, ECK ;
KOVACH, NL ;
HOYER, JR ;
SMITH, JW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (44) :26232-26238
[9]   Cancer statistics, 2005 [J].
Jemal, A ;
Murray, T ;
Ward, E ;
Samuels, A ;
Tiwari, RC ;
Ghafoor, A ;
Feuer, EJ ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2005, 55 (01) :10-30
[10]  
Kondo M, 1999, CLIN CANCER RES, V5, P4005