Schlößer Hans Anton, Drebber Uta, Urbanski Alexander, Haase Simon, Baltin Christoph, Berlth Felix, Neiß Susanne, von Bergwelt-Baildon Michael, Fetzner Ulrich Klaus, Warnecke-Eberz Ute, Bollschweiler Elfriede, Hölscher Arnulf Heinrich, Mönig Stefan Paul, Alakus Hakan
Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Institute of Pathology, University of Cologne, Cologne, Germany.
Gastric Cancer. 2017 Jan;20(1):83-91. doi: 10.1007/s10120-015-0577-x. Epub 2015 Dec 7.
Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown.
In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters.
Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis.
All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.
由于癌细胞的增殖和代谢增加,其对葡萄糖的需求量很高。细胞对葡萄糖的摄取受一组被称为葡萄糖转运蛋白家族(Glut-1至-12)的膜蛋白影响。虽然在几种类型的癌症中,Glut-1的表达增加且与生存率呈负相关,但其他葡萄糖转运蛋白对肿瘤生物学的影响却鲜为人知。
在这项回顾性研究中,对2005年至2010年间接受全胃切除术的150例患者的胃癌标本进行免疫组织化学染色,检测Glut-1、-3、-6和-10的表达情况。将Glut-1、-3、-6和-10的表达与预后以及临床和病理参数进行关联分析。
在分析的样本中,Glut-1、Glut-3、Glut-6和Glut-10的表达率分别为22.0%、66.0%、38.0%和43.3%。虽然Glut-1、-6和-10与预后无相关性,但Glut-3阳性染色与较高的国际抗癌联盟(UICC)分期及较差的预后相关。Glut-3阳性患者的平均总生存期为38.6个月,而Glut-3阴性患者为51.2个月(p<0.05)。两种或更多种分析的葡萄糖转运蛋白的共表达与较差的预后相关。在多变量分析中,Glut-3和UICC分期是显著的预后因素。
在很大比例的胃癌样本中均检测到所有分析的葡萄糖转运蛋白的表达。Glut-3与较高的UICC分期及较差的预后相关。这些发现对于针对葡萄糖代谢的治疗方法以及使用放射性标记葡萄糖的成像具有重要意义。