Fei Zai-Yi, Wang Wei-Si, Li Su-Fen, Zi Jia-Ji, Yang Li, Liu Ting, Ao Song, Liu Qian-Qian, Cui Qing-Hua, Yu Min, Xiong Wei
School of Life Sciences, Yunnan University, Kunming, China.
Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Yunnan University, Kunming, China.
J Gastrointest Oncol. 2020 Dec;11(6):1291-1304. doi: 10.21037/jgo-20-120.
Mitochondrial transcription elongation factor (TEFM) is an essential molecule that regulates the replication-transcription switch of mitochondrial DNA. TEFM modulates both transcription elongation and RNA processing in mitochondria. The purpose of the present study was to determine the association of TEFM with tumor progression and prognosis in hepatocellular carcinoma (HCC) patients.
The different protein expression level of TEFM among HCC cell lines was detected by Western blotting. The gene expression profiling interactive analysis (GEPIA) was used to dynamically analyze the mRNA expression of gene in different stages of HCC. The protein and mRNA expression levels of TEFM were detected by immunohistochemistry, Western blotting and qRT-PCR. The mRNA-SeqV2 expression of TEFM and clinical information of HCC patients were downloaded from the TCGA database by using R3.6.3 software. Next, the relationships between the expression level of TEFM and clinicopathological characteristics and the prognostic value of TEFM were analyzed. A Cox regression model was used for multivariate analysis of the factors that affected the prognosis of HCC. Finally, the association between the expression levels of TEFM and other mitochondrial regulatory genes and HCC biomarker genes was analyzed by GEPIA.
TEFM is upregulated in HCC cell lines compared to noncancerous liver cell line. TEFM protein and mRNA expression levels in HCC tissues were significantly upregulated compared with those in noncancerous liver tissues. In addition, the mRNA expression level of TEFM was significantly correlated with sex, serum AFP level, and vascular invasion (P<0.05). Further analysis showed that high expression level of TEFM was unfavorable in terms of the prognosis of patients with HCC. Cox multivariate regression analysis showed that patient age, vascular invasion, and TEFM expression were independent factors affecting the prognosis of HCC patients (P<0.05). The expression level of the TEFM gene was significantly positively correlated with the expression of multiple mitochondrial regulatory genes and biomarker genes of HCC (P<0.01, R>0).
Our findings reveal that TEFM may play an important role in the progression of HCC. More importantly, the elevated expression of TEFM may potentially predict poor overall survival (OS) and disease-free survival (DFS) in patients with HCC.
线粒体转录延伸因子（TEFM）是调节线粒体DNA复制 - 转录转换的必需分子。TEFM可调节线粒体中的转录延伸和RNA加工。本研究的目的是确定TEFM与肝细胞癌（HCC）患者肿瘤进展及预后的相关性。
通过蛋白质免疫印迹法检测HCC细胞系中TEFM的不同蛋白表达水平。利用基因表达谱交互分析（GEPIA）动态分析HCC不同阶段基因的mRNA表达。通过免疫组织化学、蛋白质免疫印迹法和qRT-PCR检测TEFM的蛋白和mRNA表达水平。使用R3.6.3软件从TCGA数据库下载TEFM的mRNA-SeqV2表达及HCC患者的临床信息。接下来，分析TEFM表达水平与临床病理特征之间的关系以及TEFM的预后价值。采用Cox回归模型对影响HCC预后的因素进行多变量分析。最后，通过GEPIA分析TEFM与其他线粒体调节基因及HCC生物标志物基因表达水平之间的关联。
与非癌性肝细胞系相比，HCC细胞系中TEFM上调。与非癌性肝组织相比，HCC组织中TEFM蛋白和mRNA表达水平显著上调。此外，TEFM的mRNA表达水平与性别、血清甲胎蛋白水平及血管侵犯显著相关（P<0.05）。进一步分析表明，TEFM高表达对HCC患者的预后不利。Cox多变量回归分析显示，患者年龄、血管侵犯和TEFM表达是影响HCC患者预后的独立因素（P<0.05）。TEFM基因的表达水平与HCC的多个线粒体调节基因和生物标志物基因的表达显著正相关（P<0.01，R>0）。
我们的研究结果表明，TEFM可能在HCC进展中起重要作用。更重要的是，TEFM表达升高可能预示HCC患者总体生存期（OS）和无病生存期（DFS）较差。
