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小儿肾上腺皮质肿瘤中葡萄糖转运蛋白1(GLUT1)的表达:预测临床行为的一个有前景的指标

GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior.

作者信息

Pinheiro Céline, Granja Sara, Longatto-Filho Adhemar, Faria André M, Fragoso Maria C B V, Lovisolo Silvana M, Bonatelli Murilo, Costa Ricardo F A, Lerário Antonio M, Almeida Madson Q, Baltazar Fátima, Zerbini Maria C N

机构信息

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.

出版信息

Oncotarget. 2017 Jul 10;8(38):63835-63845. doi: 10.18632/oncotarget.19135. eCollection 2017 Sep 8.

Abstract

BACKGROUND

Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors.

METHODS

A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays.

RESULTS

The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (=0.004), being the expression of this protein associated with shorter overall and disease-free survival (=0.004 and =0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%).

CONCLUSION

GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.

摘要

背景

鉴别小儿肾上腺皮质肿瘤的良恶性是一个具有挑战性的过程。对小儿肾上腺皮质肿瘤代谢谱的新认识可能有助于这种区分、预测预后以及识别新的治疗分子靶点。本研究的目的是在一系列小儿肾上腺皮质肿瘤中表征代谢相关蛋白MCT1、MCT2、MCT4、CD147、CD44、GLUT1和CAIX的表达情况。

方法

共纳入50例患有肾上腺皮质肿瘤的小儿患者,包括41例临床诊断为良性的肿瘤和9例临床诊断为恶性的肿瘤。采用免疫组织化学方法对组织芯片中的样本进行蛋白表达评估。

结果

免疫组织化学分析显示,与良性病变相比,恶性病变中GLUT1的质膜表达显著增加(=0.004),该蛋白的表达与较短的总生存期和无病生存期相关(分别为=0.004和=0.001)。虽然除GLUT1外的其他蛋白未观察到显著差异,但MCT1、MCT4和CD147在小儿肾上腺皮质肿瘤中高表达(约90%)。

结论

GLUT1在小儿肾上腺皮质肿瘤中表达存在差异,在临床恶性肿瘤中表达较高,且与较短生存期相关,提示该恶性肿瘤向高糖酵解表型发生代谢重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/423d/5609965/c2d44615137c/oncotarget-08-63835-g001.jpg

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