Overexpression of G6PD is associated with poor clinical outcome in gastric cancer

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.

Purification of glutathioneS-transferase isoenzymes from tumour and nontumour human stomach and inhibitory effects of some heavy metals on enzymes activities

“…When we look from a global viewpoint, we can see that gastric cancer is the fourth most common malignant tumour and the second most common cause of cancer-associated death, accounting for a guessed 1.066.543 new cases and 800.230 deaths annually. Despite advances in surgery and chemotherapy, the prognosis of gastric cancer is poor, with an estimated relative 5-year survival proportion of 10-20% in USA and European countries 3,4 . Glutathione S-transferases are the member of detoxification enzyme family and play a vital role in drug resistance in various diseases 5,6 .…”

Underinvestigated Roles of Glucose-6-Phosphate Dehydrogenase

“…In humans, G6PDH is characterized by hemolytic anemia under certain conditions and can be accompanied by chronic granulomatous disease [2,6]. Over-expression of G6PDH in Drosophila prolongs lifespan [33], while in humans such over-expression can be deleterious and favor carcinogenesis [28,52,76]. Abnormalities in regulation of G6PDH activity may lead to increased lipid biosynthesis and obesity [51,52].…”

Identification and Characterization of Novel Human Glucose-6-Phosphate Dehydrogenase Inhibitors

“…3 Several studies suggest an important role of G6PD in the pathology of various human diseases such as heart failure, type 2 diabetes, hypertension, 4 and cancer. 3,5 In the context of cancer research, glucose metabolism has been of interest for more than 80 years because of initial observations that cancer cells take up high amounts of glucose and produce high amounts of lactate. 6 Because lactate production is pronounced even under aerobic conditions, a high aerobic glycolytic rate was associated with cancer cell metabolism, which is known as the Warburg effect.…”

“…These findings are supported by the fact that mammary carcinoma cells present an increased glucose flux through the PPP in vitro. 10 Moreover, G6PD activity is increased in tumor tissues compared with normal cells, 5,11 and silencing G6PD in tumor cells results in decreased proliferation and enhanced apoptosis in vitro. 12 Very recently, it was shown that the tumor suppressor p53 regulates the PPP activity by binding to and suppressing G6PD, highlighting the impact of G6PD in cancer cells.…”