title: Distinct patterns of gene expression in hepatocellular carcinomas and adjacent non-cancerous, cirrhotic liver tissues in rats fed a choline-deficient, L-amino acid-defined diet.
abstract: Gene expression profiles of HCC and surrounding non-cancerous tissues in rats fed a CDAA diet for 70 weeks, as well as normal liver tissues, were explored using an oligonucleotide microarray for 3757 genes. A total of 146 genes were identified as differentially expressed; the affected functions including metabolism, apoptosis, cell cycling, RNA splicing, Wnt signaling, reactive oxygen species-induced stress, and fibro/cirrhogenesis. The genes were found to fit into four distinct expression patterns after classification by hierarchical and k-means clustering procedures. Notably, genes within the same functional category tended to be found within the same cluster, thus gene functions appeared to be related to their expression patterns. For example, genes encoding receptors (Fisher's exact test, P < 0.01) and cytokines (Fisher's exact test, P < 0.05) were both enriched in a cluster characterized by low expression in HCC compared to their surrounding tissues. While some of the receptors in this cluster had cell-proliferative potential, others are known to be growth-suppressive. It was noted, however, that four of the 10 receptor genes encode G-protein-coupled receptors, for which growth-suppressive potential has been reported. The seven growth factors in the same cluster included two fibroblast growth factors. The current findings suggest the possibility that genes differentially expressed in this multistep carcinogenic model may be classified into relatively few clusters according to their expression patterns, and that these clusters may be associated with gene functional categories.
authors.affiliation: Department of Pathology, Sasaki Institute, Sasaki Foundation, Chiyoda-ku, Tokyo, Japan. fuematsu@sasaki.or.jp
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Uematsu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Maki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Suzuki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Abe
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusyn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
authors.forename: Dai
authors.initials: D
authors.lastname: Nakae
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D002796:Choline Deficiency / Q000150:complications; D004032:Diet; D015972:Gene Expression Regulation, Neoplastic; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000596:Amino Acids