title: Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.
abstract: Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.
authors.affiliation: Chinese National Human Genome Center at Shanghai, 351 Guo Shou-Jing Road, Shanghai 201203, China.
authors.forename: X R
authors.initials: XR
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: Z G
authors.initials: ZG
authors.lastname: Xu
authors.forename: B Z
authors.initials: BZ
authors.lastname: Qian
authors.forename: Z D
authors.initials: ZD
authors.lastname: Zhu
authors.forename: Q
authors.initials: Q
authors.lastname: Yan
authors.forename: T
authors.initials: T
authors.lastname: Cai
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: H S
authors.initials: HS
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: Q H
authors.initials: QH
authors.lastname: Huang
authors.forename: Z H
authors.initials: ZH
authors.lastname: Cheng
authors.forename: N G
authors.initials: NG
authors.lastname: Li
authors.forename: J J
authors.initials: JJ
authors.lastname: Du
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.forename: K T
authors.initials: KT
authors.lastname: Shen
authors.forename: G
authors.initials: G
authors.lastname: Lu
authors.forename: G
authors.initials: G
authors.lastname: Fu
authors.forename: M
authors.initials: M
authors.lastname: Zhong
authors.forename: S H
authors.initials: SH
authors.lastname: Xu
authors.forename: W Y
authors.initials: WY
authors.lastname: Gu
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: X T
authors.initials: XT
authors.lastname: Zhao
authors.forename: G X
authors.initials: GX
authors.lastname: Hu
authors.forename: J R
authors.initials: JR
authors.lastname: Gu
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: Z G
authors.initials: ZG
authors.lastname: Han
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D014157:Transcription Factors