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.