title: Molecular mapping of human hepatocellular carcinoma provides deeper biological insight from genomic data.
abstract: 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.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kittaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: 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
chemical_list: D017306:Annexin A2; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human