Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral spuamous cell carcinoma
Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral spuamous cell carcinoma
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DOI：
10.1002/cncr.11159
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发表时间：
2003-02-15
期刊：
影响因子：
6.2
通讯作者：
Whiteside, TL
中科院分区：
文献类型：
--
作者：
Kunkel, M;Reichert, TE;Whiteside, TL
背景。葡萄糖转运蛋白的过表达，尤其是GLUT-1的过表达，是人类恶性肿瘤的共同特征，包括头颈癌。最近，使用[F-18] -2-氟-2脱氧-D-葡萄糖（FDG）和正电子发射断层扫描（FDG-PET）评估肿瘤中葡萄糖代谢的评估已被用来识别特别侵略性的肿瘤。作者检验了以下假设：葡萄糖转运及其新陈代谢在口服鳞状细胞癌（OSCC）的进展中起关键作用。在118例OSCC患者中，通过免疫组织学对GLUT-1表达进行了回顾性分析，并为每种患者建立了GLUT-1标记指数（LI）。手术前，FDG-PET对一组44例原发性OSCC患者进行了预期评估。为了将GLUT-1的表达与葡萄糖代谢联系起来，在31例患者的亚组中确定了FDG-PET和免疫组织学，结果与总生存率相关。与患有较高LI的OSCC患者相比，患有LI的OSCC患者的OSCC患者的生存时间明显更长（138个月比60个月； P = 0.0034）。发现GLUT-1表达是OSCC患者预后的独立标志。在通过FDG-PET评估的患者中，标准化的摄取值（SUV）低于中值5.6的患者可预测生存期更长（p <0.027），而SUV> 5.6与死亡危害增加有关。结合使用，OSCC患者的高GLUT-1水平和高SUV预测生存期较短（P <0.005）。对术前辐射做出完全反应的患者倾向于具有低葡萄糖代谢的肿瘤，这是Glut-1 Li和SUV.Concconclusions所定义的。葡萄糖转运和葡萄糖代谢都决定了糖酵解肿瘤表型，这是OSCC患者预后的显着阴性生物标志物和整体生存。
BACKGROUND. The overexpression of glucose transporters, especially of Glut-1, is a common characteristic of human malignancies, including head and neck carcinoma. Recently, the assessment of glucose metabolism in the tumor with [F-18]-2-fluoro-2 deoxy-D-glucose (FDG) and positron emission tomography (FDG-PET) has been used to identify particularly aggressive tumors. The authors tested the hypothesis that both glucose transport and its metabolism play a key role in the progression of oral squamous cell carcinoma (OSCC).METHODS. Retrospective analysis of Glut-1 expression was performed by immunohistology in 118 patients with OSCC, and a Glut-1 labeling index (LI) was established for each. A separate group of 44 patients with primary OSCC was evaluated prospectively by FDG-PET prior to surgery. To link the expression of Glut-1 with glucose metabolism, both FDG-PET and immunohistology were determined in a subgroup of 31 patients, and the results were correlated with overall survival.RESULTS. The patients who had OSCC with a low LI for Glut-1 survived significantly longer compared with patients who had OSCC with a high LI (138 months vs. 60 months; P = 0.0034). It was found that Glut-1 expression was an independent marker of prognosis in patients with OSCC. In patients who were evaluated by FDG-PET, the standardized uptake value (SUV) below the median split value of 5.6 was predictive of a longer survival (P < 0.027), whereas an SUV > 5.6 was associated with an increased hazard of death. In combination, a high Glut-1 level and a high SUV predicted shorter survival (P < 0.005) for patients with OSCC. Patients who achieved a complete response to preoperative radiation tended to have tumors with low glucose metabolism, as defined by both the Glut-1 LI and the SUV.CONCLUSIONS. Both glucose transport and glucose metabolism determine the glycolytic tumor phenotype, which is a significant negative biomarker of prognosis and overall survival in patients with OSCC.