Goals: to investigate gene expression changes associated with hepatocellular carcinoma (HCC); to identify molecular markers for diagnosis and prognosis of HCC; to determine molecular targets for therapeutic intervention. Our studies have lead to several major discoveries that have been published in high impact journals. The major accomplishments are: 1) Discover a unique gene signature of liver microenvironment to predict metastases, recurrence and prognosis. 2) Gene expression profiling reveals potential early biomarkers of HCC including those with normal serum alpha-fetoprotein and small tumors. 3) A novel prognostic classification system of hepatocellular carcinoma with potential progenitor cell origin characterized by EpCAM expression. 4) Identification of unique molecular characteristics of liver cancer stem cells. 5) A novel microRNA family critical for maintaining liver cancer stem cells. 6)A novel gender-related microRNA linked to patient outcome and therapy.