title: 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.affiliation: W2MOTIF, LLC., San Diego, California, USA. dunrui@yahoo.com
authors.forename: Dunrui
authors.initials: D
authors.lastname: Wang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Moothart
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Qian
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D016000:Cluster Analysis; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D016601:RNA-Binding Proteins; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C107585:FOXM1 protein, human; C492258:FUBP1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D016601:RNA-Binding Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D004265:DNA Helicases