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Hepatitis B virus (HBV) transgenic mice spontaneously develop hepatoma within the 20 months of life.We used these mice as natural models of hepatocellular carcinoma (HCC) development.We performed genomics and proteomics analysis simultaneously to identify the dynamic gene expression patterns.HBV transgenic mice of 6, 12 and 20-month-old and the syngeneic BALB/c mice as control were sacrificed.The total liver RNA was extracted and hybridized on an oligonucleotide chip containing 35,000 genes.And the total liver proteins were separated and identified by 2-dimensional electrophoresis (2-DE), peptide mass fingerprint (PMF), and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).