Molecular background of α-fetoprotein in liver cancer cells as revealed by global RNA expression analysis

Shigeru Saito, Hidenori Ojima, Hitoshi Ichikawa, Setsuo Hirohashi, Tadashi Kondo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

α-Fetoprotein (AFP) is considered to be a diagnostic and prognostic biomarker in hepatocellular carcinoma (HCC). However, the role of AFP in the development of HCC is presently obscure. We hypothesized that a certain set of genes is expressed in a manner coordinate with AFP, and that these genes essentially contribute to the malignant characteristics of AFP-producing HCC. To address this hypothesis, we carried out global mRNA expression analysis of 21 liver cancer cell lines that produce varying levels of AFP. We identified 213 genes whose mRNA expression levels were significantly correlated with that of AFP (P < 0.0001). These included liver-specific transcription factors for AFP and other albumin family genes. Eighteen HCC-associated genes and 11 genes associated with malignancies other than HCC showed significant correlations with AFP production levels. Genes involved in lipid catabolism, blood coagulation, iron metabolism, angiogenesis, and the Wnt and mitogen-activated protein kinase pathways were also identified. Text data mining revealed that participation in the transcription factor network could explain the connection between 78 of the identified genes. Glypican 3, which is a component of the Wnt pathway and contributes to HCC development, had the fifth highest correlation coefficient with AFP. Reactivity to specific antibodies confirmed the significant correlation between AFP and glypican 3 expression in HCC tissues. These observations suggest that AFP-producing liver cancer cells may have a unique molecular background consisting of cancer-associated genes. From this genome-wide association study, novel aspects of the molecular background of AFP were revealed, and thus may lead to the identification of novel biomarker candidates.

Original languageEnglish
Pages (from-to)2402-2409
Number of pages8
JournalCancer Science
Volume99
Issue number12
DOIs
Publication statusPublished - 2008
Externally publishedYes

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Fetal Proteins
Liver Neoplasms
Hepatocellular Carcinoma
RNA
Genes
Glypicans
Data Mining
Transcription Factors
Biomarkers
Messenger RNA
Wnt Signaling Pathway
Neoplasm Genes
Genome-Wide Association Study
Blood Coagulation
Mitogen-Activated Protein Kinases
Albumins
Iron
Lipids
Cell Line
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular background of α-fetoprotein in liver cancer cells as revealed by global RNA expression analysis. / Saito, Shigeru; Ojima, Hidenori; Ichikawa, Hitoshi; Hirohashi, Setsuo; Kondo, Tadashi.

In: Cancer Science, Vol. 99, No. 12, 2008, p. 2402-2409.

Research output: Contribution to journalArticle

Saito, Shigeru ; Ojima, Hidenori ; Ichikawa, Hitoshi ; Hirohashi, Setsuo ; Kondo, Tadashi. / Molecular background of α-fetoprotein in liver cancer cells as revealed by global RNA expression analysis. In: Cancer Science. 2008 ; Vol. 99, No. 12. pp. 2402-2409.
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