Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival

Gastric Cancer. 2017 Jan;20(1):83-91. doi: 10.1007/s10120-015-0577-x. Epub 2015 Dec 7.

Abstract

Background: Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown.

Methods: In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters.

Results: Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis.

Conclusions: All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.

Keywords: Gastric cancer; Glucose transporter; Prognosis.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • Biomarkers, Tumor / metabolism*
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Glucose Transporter Type 1 / metabolism*
  • Glucose Transporter Type 3 / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • SLC2A1 protein, human
  • SLC2A10 protein, human
  • SLC2A3 protein, human
  • SLC2A9 protein, human