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

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.

• Authors: Dunrui Wang, Daniel R Moothart, Douglas R Lowy, Xiaolan Qian
• Journal: PloS one (PLoS One) Vol. 8 Issue 4 Pg. e61262 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23620736 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• 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

Topics

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