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Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to ¹⁸F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors

Authors
 Min-Hee Cho  ;  Cheol Keun Park  ;  Minhee Park  ;  Won Kyu Kim  ;  Arthur Cho  ;  Hoguen Kim 
Citation
 PLOS ONE, Vol.10(10) : e0141413, 2015 
Journal Title
 PLOS ONE 
Issue Date
2015
MeSH
Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; DNA Mutational Analysis ; Female ; Fluorodeoxyglucose F18*/metabolism ; Gastrointestinal Neoplasms/diagnosis* ; Gastrointestinal Neoplasms/genetics ; Gastrointestinal Neoplasms/metabolism* ; Gastrointestinal Stromal Tumors/diagnosis* ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/metabolism* ; Gene Expression ; Glucose/metabolism* ; Glucose Transporter Type 1/genetics ; Glucose Transporter Type 1/metabolism ; Hexokinase/genetics ; Hexokinase/metabolism ; Humans ; Immunohistochemistry ; Isoenzymes/genetics ; Isoenzymes/metabolism ; L-Lactate Dehydrogenase/genetics ; L-Lactate Dehydrogenase/metabolism ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Middle Aged ; Mutation ; Neoplasm Grading ; Positron-Emission Tomography*/methods ; Thyroid Hormones/genetics ; Thyroid Hormones/metabolism ; Tomography, X-Ray Computed ; Tumor Burden ; Young Adult
Abstract
Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs); however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated 18F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax) cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that 18F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA). Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2) and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.
Files in This Item:
T201504448.pdf Download
DOI
10.1371/journal.pone.0141413
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Kyu(김원규)
Kim, Hogeun(김호근)
Park, Min Hee(박민희)
Park, Cheol Keun(박철근) ORCID logo https://orcid.org/0000-0001-7689-0386
Cho, Min Hee(조민희)
Cho, Arthur Eung Hyuck(조응혁) ORCID logo https://orcid.org/0000-0001-8670-2473
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156730
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