Zi Jiaji, Wang Weisi, Sun Meitao, Mei Wen, Li Sufen, Li Bin, Xiao Yang, Fei Zaiyi, Zhang Ruopeng, Yu Min, Xiong Wei
College of Basic Medical Sciences, Dali University Dali, Yunnan Province, China.
Department of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College Hangzhou Province, China.
Int J Clin Exp Pathol. 2019 May 1;12(5):1909-1920. eCollection 2019.
Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. MTERF3 is overexpressed in liver cancer, pancreatic cancer, lung cancer, and breast cancer. However, whether MTERF3 is up-regulated in brain glioma is still unclear. The aim of this study was to investigate the expression and clinicopathological significance of MTERF3 in brain glioma and to analyze its potential prognostic value in brain glioma. Immunohistochemistry, Western blot, and a semi-quantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 28 human brain glioma tissues and 10 noncancerous brain tissues. The expression data of MTERF3 and its clinical information in brain glioma were downloaded from the TCGA dataset using R 2.15.3 software. The relationship between the expression of MTERF3 and its clinicopathological characteristics and its prognostic value was analyzed. A Cox regression model was used for a multivariate analysis of the factors affecting the prognosis of brain glioma. The immunohistochemistry results showed that the MTERF3 protein is located in the cytoplasm, and the positive expression rate of the MTERF3 protein in brain glioma tissues is 64.29%. We found that the positive expression rate of the MTERF3 protein in high-grade glioma tissues (81.25%) is higher than it is in low-grade glioma tissues (41.67%). The expression levels of the MTERF3 mRNA and protein in brain glioma tissues are significantly higher than they are in the noncancerous brain tissues. Moreover, the expression of MTERF3 is significantly correlated with age, tumor type, and pathological classification (<0.05). A Kaplan-Meier analysis showed that a high expression level of MTERF3 mRNA indicated a poor prognosis (log rank <0.01). Furthermore, a multivariate Cox regression analysis showed that age and tumor type were independent prognostic factors for brain glioma patients. A GEPIA analysis suggested that the expression levels of MTERF3 are positively correlated with the TFAM, TFB1M, TFB2M, MTERF1, MTERF2, TEFM, and MFN1 genes, but negatively correlated with the PINK1 gene. The expression level of MTERF3 had no correlation with the MTERF4 gene. In conclusion, these data indicate that the expression of MTERF3 in glioma tissue samples can be used as a prognostic factor for patients with glioma and that a high MTERF3 expression correlates with a poor prognosis in glioma patients.
线粒体转录终止因子3（MTERF3）是线粒体转录的负调控因子。MTERF3在肝癌、胰腺癌、肺癌和乳腺癌中过表达。然而，MTERF3在脑胶质瘤中是否上调仍不清楚。本研究的目的是探讨MTERF3在脑胶质瘤中的表达及其临床病理意义，并分析其在脑胶质瘤中的潜在预后价值。采用免疫组织化学、蛋白质印迹法和半定量逆转录聚合酶链反应（RT-PCR）分析28例人脑胶质瘤组织和10例非癌脑组织中MTERF3的蛋白和mRNA表达水平。使用R 2.15.3软件从TCGA数据集中下载脑胶质瘤中MTERF3的表达数据及其临床信息。分析MTERF3表达与其临床病理特征的关系及其预后价值。采用Cox回归模型对影响脑胶质瘤预后的因素进行多因素分析。免疫组织化学结果显示，MTERF3蛋白位于细胞质中，脑胶质瘤组织中MTERF3蛋白的阳性表达率为64.29%。我们发现，高级别胶质瘤组织中MTERF3蛋白的阳性表达率（81.25%）高于低级别胶质瘤组织（41.67%）。脑胶质瘤组织中MTERF3 mRNA和蛋白的表达水平显著高于非癌脑组织。此外，MTERF3的表达与年龄、肿瘤类型和病理分级显著相关（<0.05）。Kaplan-Meier分析显示，MTERF3 mRNA高表达提示预后不良（对数秩检验<0.01）。此外，多因素Cox回归分析显示，年龄和肿瘤类型是脑胶质瘤患者的独立预后因素。基因表达谱交互分析（GEPIA）表明，MTERF3的表达水平与线粒体转录因子A（TFAM）、线粒体转录因子B1（TFB1M）、线粒体转录因子B2（TFB2M）、MTERF1、MTERF2、线粒体转录延伸因子（TEFM）和线粒体融合蛋白1（MFN1）基因呈正相关，但与帕金森病相关蛋白1（PINK1）基因呈负相关。MTERF3的表达水平与MTERF4基因无相关性。总之，这些数据表明，MTERF3在胶质瘤组织样本中的表达可作为胶质瘤患者的预后因素，且MTERF3高表达与胶质瘤患者预后不良相关。
