Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P 5 0.016) and a higher tumor node metastasis stage (P 5 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P 5 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density. Conclusion: Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis. (HEPATOLOGY 2012;56:2231-2241 H epatocellular carcinoma (HCC) is currently the fifth-most common solid tumor worldwide and the second leading cause of cancerrelated deaths in China.1,2 Although remarkable progress has been made in recent decades, the details of the molecular mechanisms underlying HCC carcinogenesis remain to be elucidated.2,3 Survival of patients with HCC has been improved with advancements in surgical techniques, but the median survival rate remains at approximately 50% (range, 17-69) after 5 years. 4 This unfavorable prognosis is mainly because HCC is a highly vascularized type of tumor with frequent intra-or extrahepatic metastases. Blood vessels within tumors produced by angiogenesis are responsible for the poor survival of HCC patients.3,5 Cancer classification using biomarkers may effectively define risk of recurrence, which allows for the use of appropriate treatments to acquire a better prognosis.6 But, to date, few measurable biomarkers for predicting HCC recurrence have been identified.

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