In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 26 ( 2001-12-18), p. 15089-15094
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-β-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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.241522398
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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