title: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.
abstract: Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the beta-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10,431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.
authors.affiliation: Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horie
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Ando
authors.forename: Hajime
authors.initials: H
authors.lastname: Takayasu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hisami
authors.initials: H
authors.lastname: Ando
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Suita
authors.forename: Michio
authors.initials: M
authors.lastname: Kaneko
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sasaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Hashizume
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohnuma
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D018797:Cell Cycle Proteins; D020869:Gene Expression Profiling; D015723:Gene Library; D018197:Hepatoblastoma / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics*; D009857:Oncogenes; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000509:alpha-Fetoproteins / Q000032:analysis; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000509:alpha-Fetoproteins; D000097869:Polo-Like Kinase 1