Abstract
This study aims to investigate the expression and significance of glucose-6-phosphate dehydrogenase (G6PD) in human gastric cancer progression and prognosis. Using immunohistochemistry and real-time RT-PCR assay, we identified abnormally elevated expression of G6PD in gastric cancer tissues compared to paired normal stomach mucosa tissues in 24 patients (p < 0.05). In order to investigate the correlations between G6PD and the clinicopathological features of gastric cancer, the expression of G6PD in 167 patients with gastric cancer were detected by immunohistochemistry, and the results showed that overexpression of G6PD was associated with the size of tumor (p = 0.039), depth of invasion (p = 0.039), lymph node metastasis (p = 0.044), distant metastasis (p = 0.003), TNM stage (p = 0.030), and survival rate (p = 0.010). Further, Cox multivariates analysis indicated that G6PD expression level was an independent prognostic factor for patients after radical resection (p = 0.013). In conclusion, overexpression of G6PD is closely related to progression of gastric cancer, and might be regarded as an independent predictor of poor prognosis for gastric cancer.
Similar content being viewed by others
References
Garcia M, Jemal A, Ward EM, et al. Global cancer facts and figures 2007. Atlanta: American Cancer Society; 2007.
Catalano V, Labianca R, Beretta GD, et al. Gastric cancer. Crit Rev Oncol Hematol. 2009;71(2):127–64.
Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.
Ho HY, Cheng ML, Chiu DT. Glucose-6-phosphate dehydrogenase—from oxidative stress to cellular functions and degenerative diseases. Redox Rep. 2007;12:109–18.
Kuo W, Lin J, Tang TK. Human glucose-6-phosphate dehydrogenase (G6PD) gene transforms NIH 3 T3 cells and induces tumors in nude mice. Int J Cancer. 2000;85:857–64.
Batetta B, Bonatesta RR, Sanna F, Putzolu M, Mulas MF, Collu M, et al. Cell growth and cholesterol metabolism in human glucose-6-phosphate dehydrogenase deficient lymphomononuclear cells. Cell Prolif. 2002;35:143–54.
Li D, Zhu Y, Tang Q, Huiru Lu, Li H, Yang Y, et al. A new G6PD knockdown tumor-cell line with reduced proliferation and increased susceptibility to oxidative stress. Cancer Biother Radiopharm. 2009;24:81–90.
Ohl F, Jung M, Radonić A, Sachs M, Loening SA, Jung K. Identification and validation of suitable endogenous reference genes for gene expression studies of human bladder cancer. J Urol. 2006;175:1915–20.
Langbein S, Frederiks WM, zur Hausen A, Popa J, Lehmann J, Weiss C, et al. Metastasis is promoted by a bioenergetic switch: new targets for progressive renal cell cancer. Int J Cancer. 2008;122:2422–8.
Lewandowicz GM, Britt P, Elgie AW, Williamson CJ, Coley HM, Hall AG, et al. Cellular gluathione content in vitro chemo response and the effect of BSO modulation in samples derived from patients with advanced ovarian cancer. Gynecol Oncol. 2002;85:298.
Frederiks WM, van Marle J, van Oven C, Comin-Anduix B, Cascante M. Improved localization of glucose-6-phosphate dehydrogenase activity in cells with 5-cyano-2, 3-ditolyl-tetrazolium chloride as fluorescent redox dye reveals its cell cycle-dependent regulation. J Histochem Cytochem. 2006;54:47–52.
Bokun R, Bakotin J, Milasinovic DD. Semiquantitative cytochemical estimation of glucose-6-phosphate dehydrogenase activity in benign diseases and carcinoma of the breast. Acta Cytol. 1987;31:249–52.
Hughes EC. The effect of enzymes upon metabolism, storage, and release of carbohydrates in normal and abnormal endometria. Cancer. 1976;38:487–502.
Dutu R, Nedelea M, Veluda G, Burcuket V. Cytoenzymologic investigations on carcinomas of the cervix uteri. Acta Cytol. 1980;24:160–6.
Ohl F, Jung M, Xu C, Stephan C, Rabien A, Burkhardt M, et al. Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization? J Mol Med. 2005;83:1014–24.
Zampella EJ, Bradley EL, Pretlow IG. Glucose-6-phosphate dehydrogenase: a possible clinical indicator for prostatic carcinoma. Cancer. 1982;49:384–7.
Dessi S, Batetta B, Cherchi R, Onnis R, Pisano M, Pani P. Hexomonophosphate shunt enzymes in lung tumours from normal and glucose-6-phosphate dehydrogenase-deficient subjects. Oncology. 1988;45:287–91.
Li R, Jiang C. Expression of G6PD protein in gliomas and its correlation with glioma grades. Heilongjiang Med J. 2008;32:573–5.
Sobin L, Gospodarowicz M, Wittekind C. TNM classification of malignant tumours. 7th ed. New York: Wiley; 2009.
Kekec Y, Paydas S, Tuli A, Zorludemir S, Sakman G, Seydaoglu G. Antioxidant enzyme levels in cases with gastrointestinal cancer. Eur J Intern Med. 2009;20(4):403–6.
Mathupala SP, Rempel A, Pedersen PL. Aberrant glycolytic metabolism of cancer cells: a remarkable coordination of genetic, transcriptional, post-translational, and mutational events that lead to acritical role for type II hexokinase. J Bioenerg Biomembr. 1997;29:339–43.
Vizán P, Alcarraz-Vizán G, Díaz-Moralli S, Solovjeva ON, Frederiks WM, Cascante M. Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29. Int J Cancer. 2009;124:2789–96.
Chen H, Yue JX, Yang SH, Ding H, Zhao RW, Zhang S. Over expression of transketolase-like gene1 is associated with cell proliferation in uterine cervix cancer. J Exp Clin Cancer Res. 2009;28:43.
Dessì S, Batetta B, Pani P, Barra S, Miranda F, Puxeddu P. Glucose-6-phosphate dehydrogenase (G6PD) activity in tumoral tissues of GGPD-deficient subjects affected by larynx carcinoma. Cancer Lett. 1990;53:159–62.
Yuan W, Shaobin Wu, Guo J, Chen Z, Jie Ge Pu, Yang Bin Hu, et al. Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. Cancer Biol Ther. 2010;9(9):710–6.
Tian Wang-Ni, Braunstein LD, Pang J, Stuhlmeier KM, Xi Q-C, Tian X, et al. Stanton. Importance of glucose-6-phosphate dehydrogenase activity for cell growth. J Biol Chem. 1998;273:10609–17.
Forteleoni G, Argiolas L, Farris A, Ferraris AM, Gaetani GF, Meloni T. G6PD deficiency and breast cancer. Tumori. 1988;74:665–7.
Pisano M, Cocco P, Cherchi R, Onnis R, Cherchi P. Glucose-6-phosphate dehydrogenase deficiency and lung cancer: a hospital based case-control study. Tumori. 1991;77:12–5.
Tassi S, Carta S, Delfino L, Caorsi R, Martini A, Gattorno M, et al. Altered redox state of monocytes from cryopyrinassociated periodic syndromes causes accelerated IL-1β secretion. Proc Natl Acad Sci USA. 2010;107(21):9789–94.
Park J, Choe SS, Choi AH, Kim KH, Yoon MJ, Suganami T, et al. Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals. Diabetes. 2006;55(11):2939–49.
Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23:599–622.
Wells PG, Bhuller Y, Chen CS, Jeng W, Kasapinovic S, Kennedy JC, et al. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol. 2005;207:354–66.
Polimeni M, Voena C, Kopecka J, Riganti C, Pescarmona G, Bosia A, et al. Modulation of doxorubicin resistance by the glucose 6-phosphate dehydrogenase activity. Biochem J. 2011;439(1):141–9.
Acknowledgments
We thank Hai Long for his helpful comments and Kai Wang for revising the language of this manuscript.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, J., Yuan, W., Chen, Z. et al. Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumor Biol. 33, 95–101 (2012). https://doi.org/10.1007/s13277-011-0251-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-011-0251-9