title: Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy.
abstract: OBJECTIVE
  Most cancer cells exhibit increased glycolysis. The elevated glucose transporter 1 (GLUT1) expression has been reported to be associated with resistance to therapeutic agents and a poor prognosis. We wondered whether GLUT1 expression was associated with the clinical outcome in rectal cancer after preoperative chemoradiotherapy (CRT), and whether glycolysis inhibition could represent a novel anticancer treatment.
  
  
  METHODS
  We obtained total RNA from residual cancer cells using microdissection from a total of 52 rectal cancer specimens from patients who underwent preoperative CRT. We performed transcriptional analyzes, and studied the association of the GLUT1 gene expression levels with the clinical outcomes. In addition, we examined each proliferative response of three selected colorectal cancer cell lines to a glycolysis inhibitor, 3-bromopyruvic acid (3-BrPA), with regard to their expression of the GLUT1 gene.
  
  
  RESULTS
  An elevated GLUT1 gene expression was associated with a high postoperative stage, the presence of lymph node metastasis, and distant recurrence. Moreover, elevated GLUT1 gene expression independently predicted both the recurrence-free and overall survival. In the in vitro studies, we observed that 3-BrPA significantly suppressed the proliferation of colon cancer cells with high GLUT1 gene expression, compared with those with low expression.
  
  
  CONCLUSIONS
  An elevated GLUT1 expression may be a useful predictor of distant recurrence and poor prognosis in rectal cancer patients after preoperative CRT.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. saigusa@clin.medic.mie-u.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000235:genetics* / Q000628:therapy*; D011300:Preoperative Care; D011379:Prognosis; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D005641:Tegafur / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; C495677:SLC2A1 protein, human; D005641:Tegafur; D005472:Fluorouracil
references.citation: Eur J Cancer. 2001 Jan;37(2):204-9
references.pmid: 11166147
references.citation: Clin Cancer Res. 1996 Jul;2(7):1151-4
references.pmid: 9816281
references.citation: Nat Rev Cancer. 2004 Nov;4(11):891-9
references.pmid: 15516961
references.citation: Science. 2009 Sep 18;325(5947):1555-9
references.pmid: 19661383
references.citation: BMC Cancer. 2009 Jul 20;9:241
references.pmid: 19619276
references.citation: J Biol Chem. 1991 Dec 25;266(36):24632-6
references.pmid: 1761560
references.citation: Cancer. 2001 Sep 1;92(5):1144-50
references.pmid: 11571727
references.citation: Biochim Biophys Acta. 2010 Apr;1805(2):141-52
references.pmid: 20122995
references.citation: Int J Biochem Cell Biol. 2007;39(7-8):1358-66
references.pmid: 17499003
references.citation: Biochem Biophys Res Commun. 2004 Nov 5;324(1):269-75
references.pmid: 15465013
references.citation: Cancer. 1998 Jul 1;83(1):34-40
references.pmid: 9655290
references.citation: N Engl J Med. 2004 Oct 21;351(17):1731-40
references.pmid: 15496622
references.citation: Cancer. 1993 Nov 15;72(10):2979-85
references.pmid: 8221565
references.citation: Ann Surg. 2005 May;241(5):829-36; discussion 836-8
references.pmid: 15849519
references.citation: Clin Chem. 2001 Feb;47(2):195-201
references.pmid: 11159766
references.citation: Cancer Res. 2002 Jul 15;62(14):3909-13
references.pmid: 12124317
references.citation: Cancer. 2000 Jun 15;88(12):2774-81
references.pmid: 10870060
references.citation: Cancer Res. 2001 Feb 1;61(3):1029-37
references.pmid: 11221829
references.citation: Cancer Res. 2006 Apr 15;66(8):3992-5
references.pmid: 16618717
references.citation: J Bioenerg Biomembr. 2008 Dec;40(6):607-18
references.pmid: 19067133
references.citation: Br J Cancer. 2001 Sep 1;85(5):692-6
references.pmid: 11531254
references.citation: N Engl J Med. 2006 Sep 14;355(11):1114-23
references.pmid: 16971718
references.citation: J Nucl Med. 2008 Jun;49 Suppl 2:24S-42S
references.pmid: 18523064
references.citation: J Clin Oncol. 2005 Dec 1;23(34):8688-96
references.pmid: 16246976
references.citation: Surg Today. 2010 Jun;40(6):501-6
references.pmid: 20496130
references.citation: Oncogene. 2006 Aug 7;25(34):4633-46
references.pmid: 16892078
references.citation: Eur J Cancer. 2011 May;47(8):1138-45
references.pmid: 21220198
references.citation: Int J Cancer. 2009 Dec 15;125(12):2778-82
references.pmid: 19569052
references.citation: Cancer Res. 2005 Jan 15;65(2):613-21
references.pmid: 15695406
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683