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Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus

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Abstract

Purpose: The purpose of this study was to elucidate the molecular basis of hepatocellular carcinoma (HCC) caused by genotype-C hepatitis B virus (HBV). Methods: We compared molecular profiles of 15 HCCs and five non-tumorous livers, all of which were associated with genotype-C HBV infection, using DNA microarray technology. Results: Our supervised learning identified 237 genes whose expression differed between HCCs and non-tumorous livers. This result was validated by a false discovery rate of 0%. Levels of expression of 35 and 202 genes were higher and lower, respectively, in HCCs than in non-tumorous livers. Among the 237 genes, we highlighted the top 35 upregulated and top 35 downregulated genes in tumor. Interestingly, when overlapping genes were excluded, 12 (e.g., NM23-H2, MCM7, PARP1, YWHAH, HSPB1, and MSH2) of the top 34 upregulated genes and five (e.g., MT1A and MT3) of the top 33 downregulated genes were c-myc-regulated genes. The microarray data for five randomly selected genes (MCM7, UBE2L3, PPIA, CXCL12, and ASS) were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. Conclusions: Our results indicate that many c-myc-regulated genes are involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.

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Acknowledgments

This work was supported in part by the Venture Business Laboratory, Yamaguchi University, and by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (No. 15590598)

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Authors and Affiliations

  1. Departments of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Norio Iizuka, Ryouichi Tsunedomi, Takao Tamesa, Toshimasa Okada, Kazuhiko Sakamoto, Takashi Hamaguchi & Masaaki Oka

  2. Complementary Medicine, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Norio Iizuka

  3. Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube, Yamaguchi, 755-8611, Japan

    Takanobu Miyamoto, Shunji Uchimura & Yoshihiko Hamamoto

  4. Kamakaura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200 Kajiwara, Kamakura, Kanagawa, 247-8530, Japan

    Hisafumi Yamada-Okabe

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  1. Norio Iizuka
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  2. Ryouichi Tsunedomi
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  10. Yoshihiko Hamamoto
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Correspondence to Masaaki Oka.

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Iizuka, N., Tsunedomi, R., Tamesa, T. et al. Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus. J Cancer Res Clin Oncol 132, 473–481 (2006). https://doi.org/10.1007/s00432-006-0094-8

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  • DOI: https://doi.org/10.1007/s00432-006-0094-8

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