Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data.
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 30K 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-kappaB 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.
Kittaka
Nobuyoshi
N
Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Takemasa
Ichiro
I
Takeda
Yutaka
Y
Marubashi
Shigeru
S
Nagano
Hiroaki
H
Umeshita
Koji
K
Dono
Keizo
K
Matsubara
Kenichi
K
Matsuura
Nariaki
N
Monden
Morito
M
D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002874:Chromosome Mapping; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics; D015854:Up-Regulation; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human