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BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and exhibits high morbidity and mortality in the world. We recently identified LHX3 as a preferentially expressed gene with a possible involvement in HCC. OBJECTIVE: To determine the expression, clinical relevance, prognostic significance and functions of LHX3 in HCC. MATERIALS AND METHODS: LHX3 expression was assessed in 190 cancerous and 40 adjacent non-cancerous tissues by PCR, western blot and immunohistochemistry. Associations between LHX3 expression and clinicopathological characteristics of patients were investigated. Correlations between LHX3 expression and overall survival of patients were analyzed by Kaplan-Meier and Cox-regression methods. Functional roles of LHX3 were evaluated by transwell assays. RESULTS: LHX3 expression is significantly increased in carcinoma tissues, and associated with clinical stage and metastasis of patients. LHX3 expression is much higher in the advanced-stage patients than the early-stage patients, and is sharply increased in metastasic patients. High LHX3 expression is associated with unfavorable overall survival, and is an independent prognostic factor of patients. Moreover, LHX3 is an unfavorable and independent prognostic factor unique to advanced-stage patients. Knockdown expression of LHX3 obviously inhibits tumor cell migration and invasion. CONCLUSION: LHX3 is an advanced-stage prognostic biomarker, and acts as a new potential metastatic oncogene in HCC. [ABSTRACT FROM AUTHOR]