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

Abstract

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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Abbreviations

EMT:

Epithelial-mesenchymal transition

FDG:

Fluorodeoxyglucose

HCC:

Hepatocellular carcinoma

PET:

Positron emission tomography

TLR:

Tumor-to-liver standardized uptake value ratio

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Acknowledgements

The authors thank Jisuk Kim for her help in some experiments. Tissue samples were provided by the Severance Hospital at Yonsei University College of Medicine (Seoul, South Korea).

Funding

This research was supported by the National Research Foundation of Korea (Seoul, Korea; Grant Nos. NRF-2011-0030086, NRF-2015R1D1A1A01057737, and NRF-2016R1E1A1A01943303) and was supported by an Incheon National University Research Grant (Incheon, Korea) in 2016.

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Correspondence to Mijin Yun.

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No other potential conflict of interest relevant to this article was reported.

Additional information

Misu Lee and Jeong Yong Jeon have contributed equally to this work.

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Lee, M., Jeon, J.Y., Neugent, M.L. et al. 18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma. Clin Exp Metastasis 34, 251–260 (2017). https://doi.org/10.1007/s10585-017-9847-9

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Keywords

  • 18F-Fluorodeoxyglucose positron emission tomography
  • Metastasis
  • Glucose metabolism
  • Epithelial-mesenchymal transition
  • Hepatocellular carcinoma