Prognostic impact of the combination of glucose transporter 1 and ATP citrate lyase in node-negative patients with non-small lung cancer

Lung Cancer. 2015 Jun;88(3):310-8. doi: 10.1016/j.lungcan.2015.03.004. Epub 2015 Mar 23.

Abstract

Objective: Metabolic alternations are deemed a hallmark of cancer cells. Among many metabolic pathways, glycolysis and lipogenesis are essential metabolic processes in cancer cells. In this study, we examined the prognostic impact of the combined expression of glycolysis-related glucose transporter 1 (GLUT1) and ATP-citrate lyase (ACLY), which are important molecules in lipogenesis, in patients with non-small cell lung cancer (NSCLC).

Materials and methods: GLUT1 and ACLY expression in 134 NSCLC specimens were determined by immunohistochemistry using a tissue microarray (TMA). We examined the overall survival of patients with GLUT1-, ACLY- or GLUT+ACLY-positive expression using Kaplan-Meier analysis. We analyzed the prognostic impact of combined GLUT1 and ACLY expression according to lymph node status using multivariate Cox analysis.

Results: Patients with GLUT1- or ACLY-positive expression exhibited poorer overall survival compared with GLUT1- or ACLY-negative patients. GLUT1-positive/ACLY-positive expression status was associated with the worst overall survival, in contrast with GLUT1 negative/ACLY-negative expression status, which was correlated with the best overall survival (P=0.003). GLUT1-positive/ACLY-positive expression was significantly correlated with poor prognosis in node-negative but not in node-positive patients. Multivariate Cox analysis indicated combined expression of GLUT1 and ACLY was an independent prognostic factor for overall survival in node-negative patients with NSCLC (P=0.049).

Conclusion: These results suggest that the combined expression of GLUT1 and ACLY could be a more valuable prognostic factor than their individual expression in node-negative patients with NSCLC.

Keywords: ATP-citrate lyase; Glucose transporter-1; Non-small cell lung cancer; Prognosis.

MeSH terms

  • ATP Citrate (pro-S)-Lyase / genetics
  • ATP Citrate (pro-S)-Lyase / metabolism*
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Female
  • Gene Expression
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Tumor Burden

Substances

  • Biomarkers
  • Glucose Transporter Type 1
  • ATP Citrate (pro-S)-Lyase