Wersäll Ofra Castro, Löfstedt Lina, Govorov Igor, Mints Miriam, Gabrielson Marike, Shoshan Maria
Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institute, Stockholm 171 77, Sweden.
Department of Oncology-Pathology, BioClinicum, Karolinska Institute, Solna 171 64, Sweden.
Mol Clin Oncol. 2021 Feb;14(2):42. doi: 10.3892/mco.2020.2203. Epub 2020 Dec 30.
Endometrial cancer (EC) is one of the ten most common gynecological cancers. As in most cancers, EC tumour progression involves alterations in cellular metabolism and can be associated with, for instance, altered levels of glycolytic enzymes. Mitochondrial functions and proteins are known to serve key roles in tumour metabolism and progression. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α) is a major regulator of mitochondrial biogenesis and function, albeit of varying prognostic value in different cancers. The voltage-dependent anion channel type 1 (VDAC1) regulates apoptosis as well as metabolite import and export over the mitochondrial outer membrane, and is often used for comparative quantification of mitochondrial content. Using immunohistochemistry, the present study examined protein expression levels of PGC1α and VDAC1 in tumour and paired benign tissue samples from 148 patients with EC, in order to examine associations with clinical data, such as stage and grade, Ki-67, p53 status, clinical resistance and overall survival. The expression levels of both PGC1α and VDAC1, as well as a PGC1α downstream effector, were significantly lower in tumor tissues than in benign tissues, suggesting altered mitochondrial function in EC. However, Kaplan-Meier, log rank and Spearman's rank correlation tests revealed that their expression was not correlated with survival and clinical data. Therefore, PGC1α and VDAC1 are not of major prognostic value in EC.
子宫内膜癌(EC)是十大最常见的妇科癌症之一。与大多数癌症一样,EC肿瘤进展涉及细胞代谢的改变,例如可能与糖酵解酶水平的改变有关。已知线粒体功能和蛋白质在肿瘤代谢和进展中起关键作用。转录共激活因子过氧化物酶体增殖物激活受体γ共激活因子1(PGC1α)是线粒体生物发生和功能的主要调节因子,尽管在不同癌症中的预后价值各不相同。电压依赖性阴离子通道1型(VDAC1)调节细胞凋亡以及线粒体外膜上代谢物的输入和输出,常用于线粒体含量的比较定量。本研究采用免疫组织化学方法检测了148例EC患者肿瘤及配对良性组织样本中PGC1α和VDAC1的蛋白表达水平,以研究其与临床数据(如分期、分级、Ki-67、p53状态、临床耐药性和总生存期)的相关性。肿瘤组织中PGC1α和VDAC1以及PGC1α下游效应因子的表达水平均显著低于良性组织,提示EC中线粒体功能发生改变。然而,Kaplan-Meier法、对数秩检验和Spearman秩相关检验显示,它们的表达与生存期和临床数据无关。因此,PGC1α和VDAC1在EC中不具有主要的预后价值。