title: Glyceraldehyde-3-phosphate dehydrogenase gene over expression correlates with poor prognosis in non small cell lung cancer patients.
abstract: BACKGROUND
  Glycolysis in presence of oxygen with high glucose consumption is known to be the metabolism of choice in many tumors. In lung cancer this phenomenon is routinely exploited in diagnostic PET imaging of fluorodeoxyglucose uptake, but not much is known about the prognostic capabilities of glycolysis level assessment in resected lung tumor samples.
  
  
  METHODS
  In this retrospective study, we used real time polymerase chain reaction(RQ-PCR) to assess the expression level of the gene for Glyceraldehyde 3-phosphate dehydrogenase(GAPDH), key enzyme for glucose breakdown, in tumor samples from 82 consecutive early stages resected non small cell lung cancer(NSCLC) patients. We then compared our results in six large publicly available NSCLC microarray datasets collecting data from over 1250 total patients.
  
  
  RESULTS
  In our study GAPDH gene over expression was found to be an adverse prognostic factor in early stages NSCLC (n = 82 HR = 1.30 p = 0.050). This result was confirmed in 5 of 6 public datasets analyzed: Shedden et al. 2008: n = 442 HR = 1.54 p < 0.0001; Lee et al. 2008: n = 138 HR = 1.31 p = 0.043; Tomida et al. 2009: n = 117 HR = 1.59 p = 0.004; Roepman et al. 2009: n = 172 (TPI1 gene) HR = 1.51 p = 0.009; Okayama et al. 2012: n = 226 HR = 3.19 p < 0.0001; Botling et al. 2013: n = 196 HR = 1.00 p = 0.97). Furthermore, in the large and clinically well annotated Shedden et al. microarray dataset, GAPDH hazard ratio did not change whether calculated for the whole dataset or for the subgroup of adjuvant naive patients only (n = 330 HR = 1.49 p < 0.0001).
  
  
  CONCLUSIONS
  GAPDH gene over expression in resected tumor samples is an adverse prognostic factor in NSCLC. Our results confirm the prognostic value of glucose metabolism assessment in NSCLC.
authors.affiliation: Clinical Epidemiology Division, IRCCS AOU San Martino IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. roberto.puzone@yahoo.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Puzone
authors.forename: Graziana
authors.initials: G
authors.lastname: Savarino
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Dal Bello
authors.forename: Giulia
authors.initials: G
authors.lastname: Barletta
authors.forename: Carlo
authors.initials: C
authors.lastname: Genova
authors.forename: Erika
authors.initials: E
authors.lastname: Rijavec
authors.forename: Claudio
authors.initials: C
authors.lastname: Sini
authors.forename: Alessia Isabella
authors.initials: AI
authors.lastname: Esposito
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ratto
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)