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

PLoS One. 2015 Oct 28;10(10):e0141413. doi: 10.1371/journal.pone.0141413. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Lactate Dehydrogenase 5
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Positron-Emission Tomography* / methods
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism
  • Tomography, X-Ray Computed
  • Tumor Burden
  • Young Adult

Substances

  • Biomarkers
  • Carrier Proteins
  • Glucose Transporter Type 1
  • Isoenzymes
  • Membrane Proteins
  • Thyroid Hormones
  • Fluorodeoxyglucose F18
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • HK1 protein, human
  • Hexokinase
  • Glucose

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1324; URL: http://rndhospital.khidi.or.kr/rdh) and by the Mid-career Researcher Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: 2015R1A2A2A01004835; URL: http://www.nrf.re.kr/nrf_tot_cms/index.jsp?pmisso-return2=none).