The expression of glyceraldehyde-3-phosphate dehydrogenase associated cell cycle (GACC) genes correlates with cancer stage and poor survival in patients with solid tumors

PLoS One. 2013 Apr 19;8(4):e61262. doi: 10.1371/journal.pone.0061262. Print 2013.

Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often used as a stable housekeeping marker for constant gene expression. However, the transcriptional levels of GAPDH may be highly up-regulated in some cancers, including non-small cell lung cancers (NSCLC). Using a publically available microarray database, we identified a group of genes whose expression levels in some cancers are highly correlated with GAPDH up-regulation. The majority of the identified genes are cell cycle-dependent (GAPDH Associated Cell Cycle, or GACC). The up-regulation pattern of GAPDH positively associated genes in NSCLC is similar to that observed in cultured fibroblasts grown under conditions that induce anti-senescence. Data analysis demonstrated that up-regulated GAPDH levels are correlated with aberrant gene expression related to both glycolysis and gluconeogenesis pathways. Down-regulation of fructose-1,6-bisphosphatase (FBP1) in gluconeogenesis in conjunction with up-regulation of most glycolytic genes is closely related to high expression of GAPDH in the tumors. The data presented demonstrate that up-regulation of GAPDH positively associated genes is proportional to the malignant stage of various tumors and is associated with an unfavourable prognosis. Thus, this work suggests that GACC genes represent a potential new signature for cancer stage identification and disease prognosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Case-Control Studies
  • Cell Cycle / genetics*
  • Cellular Senescence / genetics
  • Cluster Analysis
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Gluconeogenesis / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Glycolysis / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Neoplasm Staging
  • Prognosis
  • RNA-Binding Proteins
  • Survival Analysis
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • FOXM1 protein, human
  • FUBP1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • RNA-Binding Proteins
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • DNA Helicases