Upregulation of SLC2 (GLUT) family genes is related to poor survival outcomes in papillary thyroid carcinoma: Analysis of data from The Cancer Genome Atlas

Surgery. 2017 Jan;161(1):188-194. doi: 10.1016/j.surg.2016.04.050. Epub 2016 Nov 11.

Abstract

Background: The Warburg effect describes increased glucose uptake in cancer cells, and glucose transporter proteins are overexpressed in many tumors. In this study, we evaluated the expression of 14 SLC2A genes encoding glucose transporter proteins in papillary thyroid carcinoma patients.

Methods: Clinical information and gene expression data from 499 papillary thyroid carcinoma patients were downloaded from The Cancer Genome Atlas database. Correlations between SLC2 gene family (SLC2A1-14) mRNA expression levels and clinicopathologic factors were analyzed.

Results: There were 14 mortalities during follow-up (median, 21.6 months). Patient overall mortality was associated with age ≥45 years, extrathyroidal extension, higher TNM stage, and increased expression of SLC2A1, SLC2A3, and SLC2A14 mRNA. Greater SLC2A1, SLC2A3, and SLC2A14 expression was associated with increased mortality (odds ratio: 11.692, 95% confidence interval: 3.362-36.938; odds ratio: 12.725, 95% confidence interval: 4.247-40.187; and odds ratio: 13.768, 95% confidence interval: 4.208-61.710, respectively). Kaplan-Meier survival analysis indicated that overall survival was shorter in patients with high rather than low SCL2 expression (SLC2A1, P = .003; SLC2A3, P < .001; and SLC2A14, P < .001).

Conclusion: Upregulation of the SLC2A1, SLC2A3, and SLC2A14 genes was associated with increased mortality in papillary thyroid carcinoma patients, and SLC2 gene expression levels are potentially useful prognostic indicators.

MeSH terms

  • Adult
  • Carcinoma / genetics*
  • Carcinoma / mortality
  • Carcinoma / surgery
  • Carcinoma, Papillary
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Glucose Transporter Type 3 / genetics*
  • Human Genome Project
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • ROC Curve
  • Retrospective Studies
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics*
  • Survival Analysis
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / surgery
  • Thyroidectomy / methods
  • Thyroidectomy / mortality
  • Up-Regulation

Substances

  • Glucose Transporter Type 3
  • RNA, Messenger
  • SLC20A1 protein, human
  • SLC2A3 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type III