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

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages251-260
Number of pages10
JournalClinical and Experimental Metastasis
Volume34
Issue number3-4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Epithelial-Mesenchymal Transition
Fluorodeoxyglucose F18
Hepatocellular Carcinoma
Neoplasm Metastasis
Positron Emission Tomography Computed Tomography
Cell Proliferation
Glucose
Neoplasms
Cell Movement
Proteins
Therapeutics
Facilitative Glucose Transport Proteins
Positron-Emission Tomography
Protein Isoforms
Phenotype
Cell Line
Mortality
Liver
Growth
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography is associated with metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma. / Lee, Misu; Jeon, Jeong Yong; Neugent, Micheal L.; Kim, Jung Whan; Yun, Mijin.

In: Clinical and Experimental Metastasis, Vol. 34, No. 3-4, 01.04.2017, p. 251-260.

Research output: Research - peer-reviewArticle

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