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Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas

Oncogene volume 20, pages 4568–4575 (2001)Cite this article

Abstract

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

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Acknowledgements

We thank Dr Y-D Yoon for HBx plasmid and for anti HBx antibody and Dr B-K Chae for middle HBs plasmid. This work was supported by grants from the Korea National Cancer Control Program, Ministry of Health and Welfare, and the 21C Frontier Human Genome Project, The Ministry of Science and Technology, Republic of Korea.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of GI and Hepatology, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk, 561-712, Republic of Korea

    Mi-Young Kim, Jung-Hyang Park & Dae-Ghon Kim

  2. Department of Anatomical Pathology, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk, 561-712, Republic of Korea

    Woo-Sung Moon

  3. Department of General Surgery, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk, 561-712, Republic of Korea

    Back-Hwan Cho

  4. Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungpuk, 790-784, Republic of Korea

    Eun Park, Dong-Hyun Park & Hee-Sup Shin

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Kim, MY., Park, E., Park, JH. et al. Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas. Oncogene 20, 4568–4575 (2001). https://doi.org/10.1038/sj.onc.1204626

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