To investigate the expression of glucose transporter 1 (GLUT1) in colorectal cancer (CRC) and its relationship to clinicopathological variables.
Methods
The expression of GLUT1 in 163 primary tumors together with the corresponding normal mucosa, and 36 liver metastases was examined using real-time PCR.
Results
The mean value of GLUT1 was higher in primary tumors (50.390 ± 68.648) than in the corresponding normal mucosa (20.437 ± 28.703, p<0.0001), while there was no significant difference in GLUT1 expression between CRC and liver metastasis (50.390 ± 68.648 vs 52.277 ± 52.482, p=0.190). In CRCs, GLUT1 expression was higher in poorly differentiated than in well and moderately differentiated tumors (p=0.022), and higher in stage III + IV than in stage I + II tumors (p=0.035). The patients with high-expressed GLUT1 had a worse prognosis than those with low-expressed GLUT1 independently of gender, age, tumor site, stage and differentiation (p=0.026, RR 2.737, 95% CI 1.126–6.651) in stage I-III CRCs. In liver metastasis, GLUT1 expression was higher in larger tumors than in smaller ones (p=0.025).
Conclusions
Overexpression of GLUT1 in stage I-III CRCs was independently associated with poor prognosis.
StewartB.W., KleihuesP., eds. World cancer report.Lyon: IARC Press, 2003.
2.
Cancerfonden, The Swedish Cancer Society. Annual Report 2008 (Cancerfondsrapporten 2008). Available at http://www.cancerfonden.se.
3.
DeVitaV.T., HellmanS., RosenbergS.A., eds. Cancer: principles and practice of oncology.Philadelphia: Lippincott Williams and Wilkins, 2004.
4.
ColemanCN:Modulating the radiation response.Stem Cells1996; 14: 10–5.
5.
TrédanO., GalmariniC.M., PatelK., TannockIF: Drug resistance and the solid tumor microenvironment.J Natl Cancer Inst2007; 99: 1441–54.
6.
MaherF., VannucciS.J., SimpsonI.A.Glucose transporter proteins in brain.FASEB J1994; 8: 1003–11.
7.
CampsM., VilaroS., TestarX., PalacinM., ZorzanoA.High and polarized expression of GLUTI glucose transporters in epitheial cells from mammary gland: acute down-regulation of GLUT1 carriers by weaning.Endocrinology1994; 134: 924–34.
8.
JanssonT., WennergrenM., IllsleyN.P.Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation.J Clin Endocrinol Metab1993; 77: 1554–62.
9.
YounesM., LechagoL.V., LechagoJ.Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases.Clin Cancer Res1996; 2: 1151–4.
10.
HaberR.S., RathanA., WeiserK.R.GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis.Cancer1998; 83: 34–40.
11.
YounesM., LechagoL.V., SomoanoJ.R., MosharafM., LechagoJ.Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers.Cancer Res1996; 56: 1164–7.
12.
YounesM., BrownR.W., StephensonM., GondoM., CagleP.T.Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival.Cancer1997; 80: 1046–51.
13.
AirleyR.E., MobasheriA.Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics.Chemotherapy2007; 53: 233–56.
14.
MedinaR.A., OwenG.I.Glucose transporters: expression, regulation and cancer.Biol Res2002; 35: 9–26.
15.
CooperR., SariogluS., SökmenS.Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma?Br J Cancer2003; 89: 870–6.
16.
AirleyR., LoncasterJ., DavidsonS.Glucose transporter Glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix.Clin Cancer Res2001; 7: 928–34.
17.
WinterS.C., BuffaF.M., SilvaP.Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers.Cancer Res2007; 67: 3441–9.
18.
JansJ., van DijkJ.H., van SchelvenS.Expression and localization of hypoxia proteins in prostate cancer: prognostic implications after radical prostatectomy.Urology2010; 75: 786–92.
19.
ZhangH., NordenskjöldB., DufmatsM., SöderkvistP., SunX.F.K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.Eur J Cancer1998; 34: 2053–7.
20.
NakamuraY., NawataM., WakitaniS.Expression profiles and functional analyses of Wnt-related genes in human joint disorders.Am J Pathol2005; 167: 97–105.
21.
MoriM., StaniunasR.J., BarnardG.F., JessupJ.M., SteeleG.D.Jr., ChenL.B.The significance of carbonic anhydrase expression in human colorectal cancer.Gastroenterology1993; 105: 820–6.
22.
WarburgO.On the origin of cancer cells.Science1956; 123: 309–14.
23.
HatanakaM.Transport of sugars in tumor membranes.Biochem Biophys Acta1974; 355: 77–104.
24.
BrownR.S., WahlR.L.Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study.Cancer1993; 72: 2979–85.
25.
MellanenP., MinnH., GrénmanR., HärkönenP.Expression of glucose transporters in head-and-neck tumors.Int J Cancer56: 622–9, 1994.
26.
ItoT., NoguchiY., SatohS., HayashiH., InayamaY., KitamuraH.Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage.Mod Pathol1998; 11: 437–43.
27.
YamamotoT., SeinoY., FukumotoH.Over-expression of facilitative glucose transporter genes in human cancer.Biochem Biophys Res Commun1990; 170: 223–30.
28.
ChungF.Y., HuangM.Y., YehC.S.GLUT1 gene is a potential hypoxic marker in colorectal cancer patients.BMC Cancer2009; 9: 241.
29.
Van LaarhovenH.W., KaandersJ.H., LokJ.Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer.Int J Radiat Oncol Biol Phys2006; 64: 473–82.
30.
BosJ.L.ras oncogenes in human cancer: a review.Cancer Res1989; 49: 4682–9.
31.
DaviesH., BignellG.R., CoxC.Mutations of the BRAF gene in human cancer.Nature2002; 417: 949–54.
