Li Sufen, Wang Weisi, Zi Jiaji, Sun Meitao, Mei Wen, Yang Na, Zhang Ruopeng, Yu Min, Xiong Wei
College of Basic Medical Sciences, Dali University, Dali 671000, China.
Key Laboratory for Clinical Biochemistry Test of High Education in Yunnan Province, Dali University, Dali 671000, China.
Transl Cancer Res. 2020 May;9(5):3610-3622. doi: 10.21037/tcr.2020.04.16.
Mitochondrial transcription elongation factor (TEFM) is a key molecule for mitochondrial DNA (mtDNA) replication-transcription switch. TEFM regulates both transcription elongation and RNA processing in mitochondria. However, the expression level and prognostic value of TEFM in low grade glioma (LGG) remain unclear. Therefore, in this study, we aimed to evaluate the clinical significance and the prognostic value of TEFM in LGG based on publicly available data.
The relative mRNA expression level of TEFM in non-tumor brain tissues and LGG tissues were retrieved from Gene Expression Profiling Interactive Analysis (GEPIA). The RNA-Seq expression of TEFM and clinical information in LGG patients were collected from the updated the Cancer Genome Atlas (TCGA) database by using R3.6.1 software. Next, the relationship between the mRNA expression of TEFM and clinicopathological characteristics were analyzed. Kaplan-Meier survival curves of overall survival (OS) and disease-free survival (DFS) were implemented for the relationship between the mRNA expression of TEFM and the prognosis of LGG patients. A Cox regression model was performed for the multivariate analysis of the factors affected the prognosis of LGG patients. GEPIA online tool was used to analyze the correlation between gene expression level and other related mitochondrial regulatory genes in LGG. Finally, The Gene Set Enrichment Analysis (GSEA) was performed to identify cell processes and molecular signaling cascades affected by TEFM.
GEPIA analysis showed that the mRNA expression levels of TEFM in LGG were significantly higher than that of non-tumor tissue. Moreover, the mRNA expression of TEFM is significantly correlated with age, World Health Organization (WHO) grade, pathological types, headache history and supratentorial location (P<0.05). Kaplan-Meier analysis showed that a high expression level of TEFM mRNA indicated a poor prognosis in OS rate (log-rank, P<0.01). Multivariate Cox regression analysis showed that age, WHO grade, pathological types and supratentorial location were the independent prognostic factors of LGG patients. The mRNA expression levels of TEFM gene were positively correlated with the , , , and gene (P<0.01, R>0), but negatively correlated with the gene (P<0.01, R=-0.18) in LGG. The GSEA revealed that genes associated with the cell cycle, RNA degradation, spliceosome, and ubiquitin mediated proteolysis signaling pathway were remarkably enriched in higher-TEFM versus lower-TEFM tumors.
Our findings disclosed that the expression of TEFM mRNA was significantly upregulated in human LGG tissues compared to non-tumor brain tissues. More importantly, the elevated expression of TEFM mRNA may potentially predict poor OS in LGG patients.
线粒体转录延伸因子（TEFM）是线粒体DNA（mtDNA）复制 - 转录转换的关键分子。TEFM调节线粒体中的转录延伸和RNA加工。然而，TEFM在低级别胶质瘤（LGG）中的表达水平和预后价值仍不清楚。因此，在本研究中，我们旨在基于公开可用数据评估TEFM在LGG中的临床意义和预后价值。
从基因表达谱交互式分析（GEPIA）中检索非肿瘤脑组织和LGG组织中TEFM的相对mRNA表达水平。使用R3.6.1软件从更新的癌症基因组图谱（TCGA）数据库中收集LGG患者的TEFM的RNA测序表达和临床信息。接下来，分析TEFM的mRNA表达与临床病理特征之间的关系。对TEFM的mRNA表达与LGG患者预后之间的关系进行总生存（OS）和无病生存（DFS）的Kaplan-Meier生存曲线分析。对影响LGG患者预后的因素进行多变量分析的Cox回归模型。使用GEPIA在线工具分析LGG中基因表达水平与其他相关线粒体调节基因之间的相关性。最后，进行基因集富集分析（GSEA）以鉴定受TEFM影响的细胞过程和分子信号级联。
GEPIA分析显示，LGG中TEFM的mRNA表达水平显著高于非肿瘤组织。此外，TEFM的mRNA表达与年龄、世界卫生组织（WHO）分级、病理类型、头痛史和幕上位置显著相关（P<0.05）。Kaplan-Meier分析表明，TEFM mRNA的高表达水平表明OS率预后较差（对数秩，P<0.01）。多变量Cox回归分析表明，年龄、WHO分级、病理类型和幕上位置是LGG患者的独立预后因素。在LGG中，TEFM基因的mRNA表达水平与 、 、 、 和 基因呈正相关（P<0.01，R>0），但与 基因呈负相关（P<0.01，R = -0.18）。GSEA显示，与细胞周期、RNA降解、剪接体和泛素介导的蛋白水解信号通路相关的基因在高TEFM与低TEFM肿瘤中显著富集。
我们的研究结果表明，与非肿瘤脑组织相比，人LGG组织中TEFM mRNA的表达显著上调。更重要的是，TEFM mRNA表达的升高可能预示LGG患者的OS较差。
