Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy.

Abstract

PURPOSE:

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.

CONCLUSION:

An elevated GLUT1 expression may be a useful predictor of distant recurrence and poor prognosis in rectal cancer patients after preoperative CRT.

• Authors: Susumu Saigusa, Yuji Toiyama, Koji Tanaka, Yoshinaga Okugawa, Hiroyuki Fujikawa, Kohei Matsushita, Keiichi Uchida, Yasuhiro Inoue, Masato Kusunoki
• Journal: Surgery today (Surg Today) Vol. 42 Issue 5 Pg. 460-9 (May 2012) ISSN: 1436-2813 [Electronic] Japan
• PMID: 22072148 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Glucose Transporter Type 1
• Ki-67 Antigen
• SLC2A1 protein, human
• Tegafur
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Cell Line, Tumor
• Chemoradiotherapy
• Female
• Fluorouracil (administration & dosage)
• Gene Expression
• Glucose Transporter Type 1 (metabolism)
• Humans
• Ki-67 Antigen (metabolism)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (genetics, mortality, pathology)
• Neoplasm Staging
• Neoplasm, Residual (genetics, therapy)
• Preoperative Care
• Prognosis
• ROC Curve
• Rectal Neoplasms (genetics, pathology, therapy)
• Remission Induction
• Retrospective Studies
• Tegafur (administration & dosage)
• Tumor Cells, Cultured