Identification and characterization of a novel human hepatocellular carcinoma-associated gene.

To investigate liver cancer-associated genes and to explore the molecular basis of liver cancer genesis, we have cloned a novel hepatocellular carcinoma (HCC)-related gene with a transcript of 2520 base pairs in length named HCCA2 by mRNA differential display polymerase chain reaction (DDPCR) and screening a placenta cDNA library. No significant homologous protein with known genes was found. Western blot analysis showed that HCCA2 could be expressed in transfected 293 cells. Northern hybridization analysis showed that HCCA2 mRNA was expressed in 79% (34/43) patients with HCC, most of whom had significantly high expression in HCC tissues, while not expressed in corresponding noncancerous liver tissues. The clinical pathological data showed that the HCCA2 was significantly associated with the invasion of tumour capsule (P = 0.0007) and the expression of ki-67 protein (P = 0.0022). Immunohistochemical staining confirmed that the HCCA2 protein was localized in cytoplasm of liver cancer tissues. According to amino acid analysis of the protein and its localization, it may play a role in a cascade of intracellular signal transduction because the protein was characterized with two Src homology 3 (SH3) binding-domains and several functional motifs of phosphorylation.