Glyceraldehyde-3-phosphate dehydrogenase gene over expression correlates with poor prognosis in non small cell lung cancer patientsReportar como inadecuado




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Molecular Cancer

, 12:97

First Online: 29 August 2013Received: 18 April 2013Accepted: 18 June 2013DOI: 10.1186-1476-4598-12-97

Cite this article as: Puzone, R., Savarino, G., Salvi, S. et al. Mol Cancer 2013 12: 97. doi:10.1186-1476-4598-12-97

Abstract

BackgroundGlycolysis 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.

MethodsIn this retrospective study, we used real time polymerase chain reactionRQ-PCR to assess the expression level of the gene for Glyceraldehyde 3-phosphate dehydrogenaseGAPDH, key enzyme for glucose breakdown, in tumor samples from 82 consecutive early stages resected non small cell lung cancerNSCLC patients. We then compared our results in six large publicly available NSCLC microarray datasets collecting data from over 1250 total patients.

ResultsIn 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.

ConclusionGAPDH 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.

KeywordsWarburg effect GAPDH RQ-PCR Gene expression microarrays Non small cell lung cancer prognosis Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-97 contains supplementary material, which is available to authorized users.

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Autor: Roberto Puzone - Graziana Savarino - Sandra Salvi - Maria Giovanna Dal Bello - Giulia Barletta - Carlo Genova - Erika Rija

Fuente: https://link.springer.com/







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