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电压依赖性阴离子通道在子宫内膜癌中的表达及其潜在的预后意义。

Expression of voltage-dependent anion channels in endometrial cancer and its potential prognostic significance.

作者信息

Jóźwiak Paweł, Ciesielski Piotr, Forma Ewa, Kozal Karolina, Wójcik-Krowiranda Katarzyna, Cwonda Łukasz, Bieńkiewicz Andrzej, Bryś Magdalena, Krześlak Anna

机构信息

Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Łodz, Poland.

Clinical Division of Gynecological Oncology, Medical University of Lodz, Lodz, Poland.

出版信息

Tumour Biol. 2020 Aug;42(8):1010428320951057. doi: 10.1177/1010428320951057.

DOI:10.1177/1010428320951057
PMID:32829673
Abstract

The exchange of metabolites between mitochondria and cytosol occurs through pores formed by voltage-dependent anion channel proteins. Voltage-dependent anion channels appear to be master regulators of mitochondrial bioenergetics and the intracellular flow of energy. Deregulation of voltage-dependent anion channels expression is thought to be related to mitochondrial dysfunction in cancer. The aim of this study was to investigate the mRNA and protein expression levels of VDAC1, VDAC2, and VDAC3 in relation to clinicopathological characteristics of endometrial cancer as well as the prognostic significance of voltage-dependent anion channels expression for overall survival. VDAC1 and VDAC3 expressions were significantly higher in cancer compared to normal tissues. Kaplan-Meier analysis indicated that high expression of all genes or high VDAC2 protein level predicted poor overall survival. Multivariate analysis identified the VDAC1 and VDAC2 mRNA levels as well as VDAC2 protein level as independent prognostic factors. Our results suggest that increased expression of voltage-dependent anion channels correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.

摘要

线粒体与细胞质之间代谢物的交换通过电压依赖性阴离子通道蛋白形成的孔进行。电压依赖性阴离子通道似乎是线粒体生物能量学和细胞内能量流动的主要调节因子。电压依赖性阴离子通道表达失调被认为与癌症中的线粒体功能障碍有关。本研究的目的是调查VDAC1、VDAC2和VDAC3的mRNA和蛋白质表达水平与子宫内膜癌临床病理特征的关系,以及电压依赖性阴离子通道表达对总生存期的预后意义。与正常组织相比,癌症组织中VDAC1和VDAC3的表达显著更高。Kaplan-Meier分析表明,所有基因的高表达或高VDAC2蛋白水平预示着总生存期较差。多变量分析确定VDAC1和VDAC2的mRNA水平以及VDAC2蛋白水平为独立的预后因素。我们的结果表明,电压依赖性阴离子通道表达增加与肿瘤进展相关,可能作为子宫内膜癌潜在的预后生物标志物。

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