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.
Highlights
Cancer cell metabolism characterized by high glycolysis rate in presence of oxygen has been confirmed in many tumors [1]
In univariate Cox analysis, GAPDH gene expression, measured by RQ-PCR, was found significantly correlated with patient survival (HR1.30; 95%confidence interval (CI) 1.00-1.69; p = 0.050) (Figure 1A, forest plot top line)
Kaplan-Meier survival plot (Figure 2), where patients are divided by GAPDH gene expression level being higher or lower than the median level, shows that patients with lower GAPDH levels had a better survival than patients with higher GAPDH levels
Summary
Cancer cell metabolism characterized by high glycolysis rate in presence of oxygen has been confirmed in many tumors [1] The high glycolysis rate in tumors, as assessed by diagnostic positron emission tomography (PET) imaging of fluorodeoxyglucose (FDG) uptake, is exploited in clinical practice, in the differential diagnosis of nodules of unknown origin, and, more recently, in prognostic studies [5,6,7]. 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
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