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01-04-2017 | Research Paper

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

Authors: Misu Lee, Jeong Yong Jeon, Micheal L. Neugent, Jung-Whan Kim, Mijin Yun

Published in: Clinical & Experimental Metastasis | Issue 3-4/2017

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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Title: 18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma
Authors: Misu Lee
Jeong Yong Jeon
Micheal L. Neugent
Jung-Whan Kim
Mijin Yun
Publication date: 01-04-2017
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 3-4/2017
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-017-9847-9

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