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

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 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.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.

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“…Therefore, GAPDH has been widely used as a reference gene in several assays in biochemical and molecular biology, such as Northern blotting, reverse transcriptase‐polymerase chain reaction, and western blotting. More recently, the use of GAPDH as a reference gene has been questioned and challenged by several research groups, after various studies on the changes in GAPDH expression in different cancers . These previous studies suggest that GAPDH may be inaccurate when it is used for normalization of gene expression results in pre‐clinical or clinical cancer studies .…”

Glyceraldehyde-3-phosphate dehydrogenase is overexpressed in colorectal cancer onset

“…However, in these reports tumour samples were obtained from patients with advanced stages of tumour progression (II-IV) [4,23,37,38], without tumour staging classification [39] or where GAPDH gene but not protein expression was quantified [40,41]. In the present study, we have observed a significant overexpression of GAPDH protein during the tumour onset which is associated with patients in the early stages of disease (stage I) and a better outcome.…”

Glyceraldehyde-3-phosphate Dehydrogenase Is Activated by Lysine 254 Acetylation in Response to Glucose Signal

“…Proliferation-Elevated GAPDH protein levels are reported in different types of cancer cells, especially in lung cancer (4,19). As a required enzyme in glycolysis, GAPDH is essential for cell growth in vitro and in vivo.…”