title: Characterization of liver-cirrhosis nodules by analysis of gene-expression profiles and patterns of allelic loss.
abstract: To disclose genetic mechanisms involved in development or progression of hepatocellular carcinoma (HCC), we used a genome-wide cDNA microarray consisting of 8,448 genes to compare gene-expression profiles among 12 liver-cirrhosis nodules (LCNs) and five specimens of HCC excised from a single patient and carefully prepared by laser-capture microdissection (LCM). The expression patterns enabled us to identify 72 genes that were frequently upregulated and 57 that were downregulated specifically in the LCN specimens as compared to the HCCs. We also documented upregulation of 31 genes and downregulation of seven others in both HCC and LCN tissues. Several types of intracellular kinase, including receptor-type kinase, were upregulated in LCNs. Expression patterns of HCCs and LCNs generally represented two genetically distinct groups when subjected to a hierarchical clustering analysis, although expression profiles of two of the LCNs resembled the HCC pattern. Analysis of allelic losses at microsatellite loci revealed that LCNs showed frequent loss of heterozygosity (LOH) (33%) in chromosomal regions 6q and 22q; over half of the LCNs had lost an allele for at least one of the 28 loci examined. The presence of early genetic changes among LCNs, with additional genetic changes occurring during formation of HCCs, suggests that hepatocellular carcinogenesis follows the multistep model established for colon cancers and that some LCNs may be precancerous lesions.
authors.affiliation: Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-0063, Japan.
authors.forename: Hisaki
authors.initials: H
authors.lastname: Nagai
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Terada
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
authors.forename: Aya
authors.initials: A
authors.lastname: Yabe
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Onda
authors.forename: Takemitsu
authors.initials: T
authors.lastname: Nagahata
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.forename: Masaharu
authors.initials: M
authors.lastname: Minegishi
authors.forename: Maya
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Baba
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D042282:Microdissection / Q000379:methods; D018895:Microsatellite Repeats; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis