Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival

Abstract

Background Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown. Methods In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters. Results Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p \ 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis. Conclusions All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.

Glucose transporter 1 regulates the proliferation and cisplatin sensitivity of esophageal cancer

“…GLUT1 and glycolytic enzymes associated with catabolizing glucose are transcriptionally regulated by HIF1A and MYC oncogenes such as HIF1A and MYC, which are activated in cancers with increased GLUT1 expression. GLUT3 expression has also been associated with poor prognosis in various cancers . However, we did not detect a compensatory upregulation of GLUT3 expression in ESCC cells after inhibiting GLUT1.…”

“…GLUT3 expression has also been associated with poor prognosis in various cancers. 23 However, we did not detect a compensatory upregulation of GLUT3 expression in ESCC cells after inhibiting GLUT1. In contrast, HK2, which catalyzes the conversion of glucose to glucose-6-phosphate, was upregulated in GLUT1silenced cells.…”

The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis

“…All of the included studies measured the expression of GLUT1 by means of immunohistochemistry (IHC) staining or PCR in human tissues, and the cut-off values varied across studies. Among the studies, 4 evaluated lung cancer [5–8], 3 evaluated pancreatic cancer [9–11], 3 evaluated breast cancer [12, 14], 2 evaluated gallbladder cancer [10, 15], 2 evaluated gastric cancer [16, 17], 2 evaluated colorectal cancer [18, 19], 2 evaluated laryngeal cancer [20, 21], and 1 each evaluated hypopharyngeal cancer [22], endometrial cancer [23], salivary gland tumor [24], adrenocortical cancer [25], liver cancer [26], ampulla of Vater cancer [10], extrahepatic bile duct cancer [10], oral cancer [27], neuroblastic tumors [28], cervical cancer [29], ovarian cancer [30] and esophageal cancer [31]. Due to the retrospective design of the included studies, only five studies examined both OS and DFS [6, 12, 14, 25, 29].…”

“…Some studies indicated that there was a poor prognostic value of GLUT1 in oral squamous cell carcinoma [27], malignant salivary gland tumors [24], colorectal cancer [18, 19], gastric cancer [16, 17], gallbladder cancer [10, 15], extrahepatic bile duct cancer [10], adrenocortical carcinoma [25] and neuroblastic tumor [28]. Others studies found there was no significant association between GLUT1 expression with prognosis in laryngeal cancer [20, 21], ampulla of vater cancer [10], extrahepatic bile duct cancer [10], cervical cancer [29], and ovarian cancer [2].…”

Preoperative staging of nodal status in gastric cancer

“…More recent studies indicate that appropriate patient selection can lead to a significant improvement of the accuracy of using FDG-PET-CT for lymph node assessment (27,28). For such patient selection, it seems beneficial to include extra features such as GLUT-1 expression; this glucose transporter molecule is important in gastric cancer glucose metabolism (37)(38)(39). Other tracers used for PET did not demonstrate reproducible benefits for determining staging so far.…”