Correlation of IDH1 and B7-H3 expression with prognosis of CRC patients

Correlation of IDH1 and B7-H3 expression with prognosis of CRC patients
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IDH1、B7-H3表达与CRC患者预后的相关性

DOI:
10.1016/j.ejso.2018.05.005
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发表时间:
2018-08-01
期刊:
影响因子:
3.8
通讯作者:
Hua, Dong
Hua, Dong
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Jingyi;Wang, Fang;Hua, Dong

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背景:B7-H3是一种免疫刺激糖蛋白,在癌症中过度表达。然而,它在癌症发生和发展中的功能作用还不是很清楚。在一些报道中,B7-H3被证明重新编程脂代谢和调节糖代谢。异柠檬酸脱氢酶1(IDH1)是TCA循环中的一种代谢酶,其反应产物参与脂质的合成。因此,我们旨在寻找一种新的标志物来预测结直肠癌患者的预后,并探讨IDH1与B7-H3的关系。方法:应用免疫组织化学方法检测225例结直肠癌组织中IDH1和B7-H3的表达水平。结果:225例组织中,IDH1和B7-H3的阳性表达率分别为37.8%(85/225)和87.6%(197/225)。在结直肠癌组织中,IDH1与B7-H3的表达显著相关(P=0.044)。多因素分析显示,B7-H3和IDH1的高表达和肿瘤分级与结直肠癌的预后有关。Kaplan-Meier生存分析显示,IDH1和B7-H3共表达的患者总体生存较差。在高表达B7-H3的SW480-B7-H3-EGFP细胞中,IDH1表达上调。结论:虽然IDH1和B7-H3不能作为独立的预后因素,但IDH1和B7-H3的共同表达与结直肠癌患者的预后显著相关,可作为联合预测指标。因此,IDH1和B7-H3之间的相关性已经在体内和体外得到了证实。(C)爱思唯尔有限公司出版的2018年。
Background: B7-H3 is an immuno-stimulatory glycoprotein that is overexpressed in cancer. However, its functional contributions to cancer development and progression are not well understood. In several reports, it was demonstrated that B7-H3 reprograms lipid metabolism and regulates glucose metabolism. Isocitrate dehydrogenase 1 (IDH1), a metabolic enzyme in the TCA cycle, its reaction product is involved in lipid synthesis. Thus, we aimed to identify a novel marker to predict the prognosis of CRC patients and to investigate the relationship between IDH1 and B7-H3.Methods: We analyzed IDH1 and B7-H3 expression levels in 225 CRC specimens by immunochemistry. Moreover, in vitro studies were performed to demonstrate the correlation between IDH1 and B7-H3.Results: Among 225 tissues, the positive rates of IDH1 and B7-H3 were 37.8% (85/225) and 87.6% (197/225), respectively. In CRC samples, IDH1 significantly correlated with B7-H3 expression (P = 0.044). Moreover, multivariate analyses revealed that high expression of both B7-H3 and IDH1 and a high tumor grade were related to the prognosis of CRC patients. Kaplan-Meier survival analysis revealed that patients with co-expression of IDH1 and B7-H3 had a poor overall survival. In SW480-B7-H3-EGFP cells, which highly express B7-H3, IDH1 was up-regulated. Similarly, knockdown of B7-H3 expression in Caco-2-shB7-H3 contributed to reduced IDH1 levels.Conclusions: Although IDH1 and B7-H3 cannot be used as independent prognostic factors, co-expression of IDH1 and B7-H3 significantly correlated with the prognosis of CRC patients and may serve as a combined predictive marker. Thus, the correlation between IDH1 and B7-H3 has been proven in vivo and in vitro. (C) 2018 Published by Elsevier Ltd.