Lee Misu, Jeon Jeong Yong, Neugent Micheal L, Kim Jung-Whan, Yun Mijin
Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, 120-752, South Korea.
Division of Life Science, College of Life Science and Bioengineering, Incheon National University, Incheon, 406-772, South Korea.
Clin Exp Metastasis. 2017 Apr;34(3-4):251-260. doi: 10.1007/s10585-017-9847-9. Epub 2017 Apr 20.
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. Several studies have investigated the relationship between F-fluorodeoxyglucose (F-FDG) uptake on positron emission tomography and the prognosis of patients with HCC, although the relationship between F-FDG uptake and expression of EMT-related proteins in these patients remains unclear. We retrospectively enrolled 116 patients with HCC treated by curative surgical resection and who underwent F-FDG positron emission tomography/computed tomography (PET/CT) for preoperative staging. The relationship between the tumor-to-liver standardized uptake value ratio (TLR) and the presence of metastasis was determined. By using HCC cell lines with different F-FDG uptake, we assessed the effect of F-FDG uptake on in vitro cell proliferation and migration on the inhibition of glucose uptake. Ten (29.4%) of 34 patients with high TLRs had extrahepatic metastases, whereas six (7.3%) of 82 patients with low TLRs had extrahepatic metastases (p = 0.002). Hepatocellular carcinomas with high TLRs showed higher expression of glucose transporter isoform 1 and EMT markers than did HCCs with low TLRs. After treatment with a glucose uptake inhibitor, HCC cells with high F-FDG uptake showed decreased cell proliferation and migration and a reversal in the expression of EMT markers. High F-FDG uptake on PET/CT is associated with frequent extrahepatic metastasis and EMT in patients with HCC. Inhibition of glucose uptake reduced cell proliferation, reversed EMT-related protein expression, and decreased cellular migration. Glycolytic regulation could be a new therapeutic target to reduce tumor growth and metastatic potential in HCCs with a high glycolytic phenotype.
肝细胞癌（HCC）是全球癌症死亡的第五大主要原因。多项研究调查了正电子发射断层扫描上的F-氟脱氧葡萄糖（F-FDG）摄取与HCC患者预后之间的关系，尽管F-FDG摄取与这些患者中EMT相关蛋白表达之间的关系仍不清楚。我们回顾性纳入了116例接受根治性手术切除且术前行F-FDG正电子发射断层扫描/计算机断层扫描（PET/CT）进行术前分期的HCC患者。确定了肿瘤与肝脏标准化摄取值比（TLR）与转移情况之间的关系。通过使用具有不同F-FDG摄取的HCC细胞系，我们评估了F-FDG摄取对体外细胞增殖和迁移以及葡萄糖摄取抑制的影响。34例高TLR患者中有10例（29.4%）发生肝外转移，而82例低TLR患者中有6例（7.3%）发生肝外转移（p = 0.002）。高TLR的肝细胞癌比低TLR的肝细胞癌表现出更高的葡萄糖转运蛋白异构体1和EMT标志物表达。在用葡萄糖摄取抑制剂治疗后，高F-FDG摄取的HCC细胞显示细胞增殖和迁移减少，EMT标志物表达逆转。PET/CT上的高F-FDG摄取与HCC患者肝外转移频繁和EMT相关。葡萄糖摄取抑制降低了细胞增殖，逆转了EMT相关蛋白表达，并减少了细胞迁移。糖酵解调节可能是减少具有高糖酵解表型的HCC肿瘤生长和转移潜能的新治疗靶点。
