Abstract 4407: Glucose transporter 1 is associated with proliferation and prognosis on esophageal squamous cell carcinoma
Authors: Sawayama Hiroshi , Iwatsuki Masaaki , Yoshida Naoya , Baba Yoshifumi , Sakamoto Yasuo , Kinoshita Koichi , Nakamura Kenichi , Kuroda Daisuke , Tsugio Eto , Toihata Tasuku , Uchihara Tomoyuki , Oda Eri , Yagi Taisuke , Ohuchi Mayuko , Ishimoto Takatugu , Baba Hideo 
Published: July 2017

Purpose: Cancer cells exhibit altered glucose metabolism, termed glycolysis which is described by the increased uptake of glucose and the conversion of glucose to lactate in cancer cells under adequate oxygen tension. Alternating glucose transporters (GLUTs) expression was detected in the cancer specific metabolism to adapt to the rapid growth and tumor microenvironment in diverse malignant tumors. In this study, GLUTs profiling of ESCC patients, the relation between proliferation and GLUT1 expression using siRNA for GLUT1 were analyzed. Furthermore, the prognostic features according to GLUT1 expression was evaluated on esophageal squamous cell carcinoma (ESCC) patients.

Methods: The ratio of the 11 GLUTs (GLUT1- GLUT14) expression between tumor and normal tissue (T/N) were analyzed in silico (GDS3838). GLUT1 expression was down-regulated using 3 siRNAs in vitro. Immunohistochemical staining of GLUT1 was performed using paraffin sections of tissues obtained from 145 resectable ESCC patients without preoperative treatment.

Results: Expression of GLUT1 (T/N 2.44; 95% confidence interval (CI): 1.78-3.34, P&lt;0.001), GLUT3 (T/N 1.96; 95%CI: 1.23-3.13, P=0.01) and GLUT6 (T/N 1.31; 95%CI: 1.12-1.54, P&lt;0.001) increased in tumor tissue compared with normal tissue. TE-1 and TE-8 cells were treated with 3 siRNAs for GLUT1 and control siRNA for 72 hours in vitro. The proliferation of TE-1 and TE-8 cells after siRNAs for GLUT1 compared with control siRNA decreased 72.9-84.5% and 44.8-53.3%, respectively. GLUT1 expression was evaluated with 145 ESCC patients. Glut1 positivity was observed in 41 patients (28.2%) and associated with depth of invasion (odds ratio (OR)=2.984; 95%CI: 1.208-7.371, P=0.018) and vascular invasion (OR=2.771; 95% CI: 1.118-6.871, P=0.028) in multivariate analysis. GLUT1 positivity was a significant disadvantage to both relapse-free survival (hazard ratio (HR)=2.021; 95%CI: 1.100-3.712; P=0.023) and esophageal cancer-specific survival (HR=2.223; 95%CI: 1.121-4.411; P=0.022) in univariate Cox hazard analysis.

Conclusions: GLUTs expression was altered in ESCC patients and GLUT1 expression was most up-regulated among the 11 GLUTs. Growth assay with siRNAs for GLUT1 revealed that GLUT1 played a curial role of ESCC cells proliferation. High expression of GLUT1 was associated with depth of invasion and poor prognosis of ESCC patients. These findings provide evidence of the significance of GLUT1 expression as a biomarker and GLUT1 may be therapeutic target in ESCC patient.

Citation Format: Hiroshi Sawayama, Masaaki Iwatsuki, Naoya Yoshida, Yoshifumi Baba, Yasuo Sakamoto, Koichi Kinoshita, Kenichi Nakamura, Daisuke Kuroda, Eto Tsugio, Tasuku Toihata, Tomoyuki Uchihara, Eri Oda, Taisuke Yagi, Mayuko Ohuchi, Takatugu Ishimoto, Hideo Baba. Glucose transporter 1 is associated with proliferation and prognosis on esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4407. doi:10.1158/1538-7445.AM2017-4407