Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lu,Kai; Yang,Jian; Li,De‑Chun; He,Song‑Bing; Zhu,Dong‑Ming; Zhang,Li‑Feng; Zhang,Xu; Chen,Xiao‑Chen; Zhang,Bing; Zhou,Jian

doi:10.3892/ol.2016.4586

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Authors:
- Kai Lu
- Jian Yang
- De‑Chun Li
- Song‑Bing He
- Dong‑Ming Zhu
- Li‑Feng Zhang
- Xu Zhang
- Xiao‑Chen Chen
- Bing Zhang
- Jian Zhou
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090. P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: May 16, 2016 https://doi.org/10.3892/ol.2016.4586
Pages: 243-249

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Abstract

Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT‑1 expression and clinicopathological factors, 18F‑fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT‑1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki‑67 expression. The receiver operating characteristic curve analysis indicated that a cut‑off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT‑1 expression. In addition, as the expression of GLUT‑1 was found to correlate with Ki‑67 expression, GLUT‑1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT‑1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Ryan DP, Hong TS and Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med. 371:1039–1049. 2014. View Article : Google Scholar : PubMed/NCBI
3	Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI
4	Diener MK, Combs SE and Buchler MW: Chemoradiotherapy for locally advanced pancreatic cancer. Lancet Oncol. 14:269–270. 2013. View Article : Google Scholar : PubMed/NCBI
5	Finger EC and Giaccia AJ: Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metastasis Rev. 29:285–293. 2010. View Article : Google Scholar : PubMed/NCBI
6	Matsumoto S, Yasui H, Mitchell JB and Krishna MC: Imaging cycling tumor hypoxia. Cancer Res. 70:10019–10023. 2010. View Article : Google Scholar : PubMed/NCBI
7	Milane L, Ganesh S, Shah S, Duan ZF and Amiji M: Multi-modal strategies for overcoming tumor drug resistance: Hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology. J Control Release. 155:237–247. 2011. View Article : Google Scholar : PubMed/NCBI
8	Thorens B and Mueckler M: Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab. 298:E141–E145. 2010. View Article : Google Scholar : PubMed/NCBI
9	Adekola K, Rosen ST and Shanmugam M: Glucose transporters in cancer metabolism. Curr Opin Oncol. 24:650–654. 2012. View Article : Google Scholar : PubMed/NCBI
10	Szablewski L: Expression of glucose transporters in cancers. Biochim Biophys Acta. 1835:164–169. 2013.PubMed/NCBI
11	Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A and Brys M: Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res. 18:721–728. 2012. View Article : Google Scholar : PubMed/NCBI
12	Wincewicz A, Sulkowska M, Koda M, Kanczuga-Koda L, Witkowska E and Sulkowski S: Significant coexpression of GLUT-1, Bcl-xL and Bax in colorectal cancer. Ann N Y Acad Sci. 1095:53–61. 2007. View Article : Google Scholar : PubMed/NCBI
13	Chiba I, Ogawa K, Morioka T, Shimoji H, Sunagawa N, Iraha S, Nishimaki T, Yoshimi N and Murayama S: Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy. Oncol Lett. 2:21–28. 2011.PubMed/NCBI
14	Ohba S, Fujii H, Ito S, Fujimaki M, Matsumoto F, Furukawa M, Yokoyama J, Kusunoki T, Ikeda K and Hino O: Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis. J Oral Pathol Med. 39:74–78. 2010. View Article : Google Scholar : PubMed/NCBI
15	Brophy S, Sheehan KM, McNamara DA, Deasy J, Bouchier-Hayes DJ and Kay EW: GLUT-1 expression and response to chemoradiotherapy in rectal cancer. Int J Cancer. 125:2778–2782. 2009. View Article : Google Scholar : PubMed/NCBI
16	Rastogi S, Banerjee S, Chellappan S and Simon GR: Glut-1 antibodies induce growth arrest and apoptosis in human cancer cell lines. Cancer Lett. 257:244–251. 2007. View Article : Google Scholar : PubMed/NCBI
17	Alakus H, Batur M, Schmidt M, Drebber U, Baldus SE, Vallböhmer D, Prenzel KL, Metzger R, Bollschweiler E, Hölscher AH and Mönig SP: Variable 18F-fluorodeoxyglucose uptake in gastric cancer is associated with different levels of GLUT-1 expression. Nucl Med Commun. 31:532–538. 2010.PubMed/NCBI
18	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
19	Reynolds T: Declaration of Helsinki revised. J Natl Cancer Inst. 92:1801–1803. 2000. View Article : Google Scholar : PubMed/NCBI
20	Böhning D, Böhning W and Holling H: Revisiting Youden's index as a useful measure of the misclassification error in meta-analysis of diagnostic studies. Stat Methods Med Res. 17:543–554. 2008. View Article : Google Scholar : PubMed/NCBI
21	Cho H, Lee YS, Kim J, Chung JY and Kim JH: Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Invest. 31:607–615. 2013. View Article : Google Scholar : PubMed/NCBI
22	Sulkowska M, Wincewicz A, Sulkowski S, Koda M and Kanczuga-Koda L: Relations of TGF-beta1 with HIF-1 alpha, GLUT-1 and longer survival of colorectal cancer patients. Pathology. 41:254–260. 2009. View Article : Google Scholar : PubMed/NCBI
23	Mayer A, Schmidt M, Seeger A, Serras AF, Vaupel P and Schmidberger H: GLUT-1 expression is largely unrelated to both hypoxia and the Warburg phenotype in squamous cell carcinomas of the vulva. BMC Cancer. 14:7602014. View Article : Google Scholar : PubMed/NCBI
24	Melstrom LG, Salabat MR, Ding XZ, Strouch MJ, Grippo PJ, Mirzoeva S, Pelling JC and Bentrem DJ: Apigenin down-regulates the hypoxia response genes: HIF-1α, GLUT-1 and VEGF in human pancreatic cancer cells. J Surg Res. 167:173–181. 2011. View Article : Google Scholar : PubMed/NCBI
25	Fraga A, Ribeiro R and Medeiros R: Tumor hypoxia: The role of HIF. Actas Urol Esp. 33:941–951. 2009. View Article : Google Scholar : PubMed/NCBI
26	Pugachev A, Ruan S, Carlin S, Larson SM, Campa J, Ling CC and Humm JL: Dependence of FDG uptake on tumor microenvironment. Int J Radiat Oncol Biol Phys. 62:545–553. 2005. View Article : Google Scholar : PubMed/NCBI
27	Huang T, Civelek AC, Li J, Jiang H, Ng CK, Postel GC, Shen B and Li XF: Tumor microenvironment-dependent 18F-FDG, 18F-fluorothymidine, and 18F-misonidazole uptake: A pilot study in mouse models of human non-small cell lung cancer. J Nucl Med. 53:1262–1268. 2012. View Article : Google Scholar : PubMed/NCBI
28	Jiang J, Tang YL and Liang XH: EMT: A new vision of hypoxia promoting cancer progression. Cancer Biol Ther. 11:714–723. 2011. View Article : Google Scholar : PubMed/NCBI
29	Osinsky S, Zavelevich M and Vaupel P: Tumor hypoxia and malignant progression. Exp Oncol. 31:80–86. 2009.PubMed/NCBI
30	Lee HE, Kim MA, Lee BL and Kim WH: Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancer. J Surg Oncol. 102:201–206. 2010. View Article : Google Scholar : PubMed/NCBI
31	Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell'Orto P, Maiorano E, MacGrogan G, Braye SG, Ohlschlegel C, et al: Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: Results from breast international group trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 26:5569–5575. 2008.