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葡萄糖代谢相关基因GLUT1在结直肠癌发生及预后中的作用

Role of glucose metabolism related gene GLUT1 in the occurrence and prognosis of colorectal cancer.

作者信息

Feng Wenming, Cui Ge, Tang Cheng-Wu, Zhang Xiao-Lan, Dai Chuang, Xu Yong-Qiang, Gong Hui, Xue Tao, Guo Hui-Hui, Bao Ying

机构信息

Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province, P.R. China.

Department of Pathology, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province, P.R. China.

出版信息

Oncotarget. 2017 May 23;8(34):56850-56857. doi: 10.18632/oncotarget.18090. eCollection 2017 Aug 22.

Abstract

Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide. However, the functional and causal SNPs for CRC remain to be mined. Glucose transporter 1 (GLUT1), a pivotal rate-limiting element in the transport of glucose in malignancy cells, has been identified to be associated with many cancers. Here, we aim to explore the role of GLUT1 in the occurrence and prognosis of colorectal cancer in a Chinese population. We found that GLUT1 expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2.11, 95% CI = 1.33-3.34, P=0.001). For a functional polymorphism of GLUT1 (rs710218), we found that individuals with TT genotype (OR = 1.68, 95% CI = 1.02-2.75, P = 0.041) or AT genotype (OR = 1.47, 95% CI = 1.09-1.99, P = 0.012) of rs710218 had a significantly increased risk of CRC compared to those with AA homozygote. These findings strongly suggest that glucose metabolism related gene GLUT1, and its functional SNP, rs710218 might contribute to CRC susceptibility and prognosis, and the exact biological mechanism awaits further research.

摘要

结直肠癌(CRC)是全球男性中第三大最常被诊断出的癌症,在女性中则为第二大。然而,CRC的功能性和因果性单核苷酸多态性(SNP)仍有待挖掘。葡萄糖转运蛋白1(GLUT1)是恶性肿瘤细胞中葡萄糖转运的关键限速因子,已被确定与多种癌症有关。在此,我们旨在探讨GLUT1在中国人群结直肠癌发生和预后中的作用。我们发现,CRC肿瘤组织中GLUT1的表达水平显著高于相应的相邻正常组织,并且Cox多变量分析表明,GLUT1表达是CRC的一个独立预后因素(风险比[HR]=2.11,95%置信区间[CI]=1.33-3.34,P=0.001)。对于GLUT1的一个功能性多态性(rs710218),我们发现rs710218的TT基因型个体(比值比[OR]=1.68,95%CI=1.02-2.75,P=0.041)或AT基因型个体(OR=1.47,95%CI=1.09-1.99,P=0.012)患CRC的风险相比AA纯合子个体显著增加。这些发现有力地表明,葡萄糖代谢相关基因GLUT1及其功能性SNP rs710218可能与CRC易感性和预后有关,确切的生物学机制有待进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83c7/5593607/9ee77565fced/oncotarget-08-56850-g001.jpg

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