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18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma

 Misu Lee  ;  Jeong Yong Jeon  ;  Micheal L. Neugent  ;  Jung-Whan Kim  ;  Mijin Yun 
 CLINICAL & EXPERIMENTAL METASTASIS, Vol.34(3~4) : 251-260, 2017 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/metabolism* ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/secondary* ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition* ; Female ; Fluorodeoxyglucose F18/metabolism* ; Follow-Up Studies ; Humans ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology* ; Male ; Middle Aged ; Multimodal Imaging/methods ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/methods* ; Prognosis ; Radiopharmaceuticals/metabolism ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured
18F-Fluorodeoxyglucose positron emission tomography ; Epithelial-mesenchymal transition ; Glucose metabolism ; Hepatocellular carcinoma ; Metastasis
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. Several studies have investigated the relationship between 18F-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography and the prognosis of patients with HCC, although the relationship between 18F-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 18F-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 18F-FDG uptake, we assessed the effect of 18F-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 18F-FDG uptake showed decreased cell proliferation and migration and a reversal in the expression of EMT markers. High 18F-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.
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1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Misu(이미수)
Jeon, Jeong Yong(전정용)
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