Research ArticleProliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis

Background & AimsThis study investigated the relationship between tumor proliferative activity and the grade of tumor glucose metabolism or angiogenesis in hepatocellular carcinoma (HCC).MethodsThe study was performed as a retrospective analysis of 63 patients with HCC who underwent fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) as a preoperative examination prior to liver resection. Tumor proliferative activity was evaluated by the Ki-67 labeling index (LI). The grade of tumor glucose metabolism was evaluated by measuring the protein expression level of glucose transporter (GLUT)-1, expression level of pyruvate kinase type M2 (PKM2) mRNA, and FDG uptake. The grade of tumor angiogenesis was evaluated by the protein expression level of vascular endothelial growth factor (VEGF) and tumor microvessel density.ResultsAll patients were divided into tertiles according to the Ki-67 LI: the low LI group (n = 21), the intermediate LI group (n = 21), and the high LI group (n = 21). The high LI group showed a tendency to have advanced tumor stage, and lower disease-free survival and overall survival rates than the low LI and the intermediate LI groups. The expression grade of GLUT-1, PKM2 mRNA, and FDG uptake gradually increased with the Ki-67 LI. On the other hand, the protein expression grade of VEGF and microvessel density was paradoxically decreased with the Ki-67 LI.ConclusionsThese data suggest that (1) the proliferative activity of a resected specimen predicted the prognosis in patients with HCC; (2) the proliferative activity was closely correlated with the glucose metabolism, but not with angiogenesis.