Elevated expression of mitochondrial transcription elongation factor (TEFM) predicts poor prognosis in low grade glioma—an analysis of the Cancer Genome Atlas (TCGA) dataset

Abstract

Background 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. Methods 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 TEFM 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. Results 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 TFAM , TFB1M , TFB2M , MTERF1–F4 and NRF1 gene (P<0.01, R>0), but negatively correlated with the POLRMT 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. Conclusions 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 ...

Cell-specific modulation of mitochondrial respiration and metabolism by the pro-apoptotic Bcl-2 family members Bax and Bak

“…The importance of TEFM in transcription of mtDNA is supported by reports that its genetic elimination caused lethality during mouse embryogenesis and that its inactivation in the heart resulted in severe cardiomyopathy in adult mice [52]. Its important role in the regulation of expression of mitochondrial genes has also pathophysiological consequences, as its increased expression promotes tumour growth and metastases and predicts poor prognosis and survival of hepatocellular carcinomas and glioma patients [53][54][55]. Moreover, TEFM variants cause early onset of neurological diseases such as mitochondrial encephalomyopathy, epilepsy and others [56].…”

Comprehensive analysis of the ability of the Cuproptosis- related gene signature to predict the prognosis of patients with pediatric acute myeloid leukemia

“…Moreover, TEFM is a key molecule for the mitochondrial DNA (mtDNA) replication-transcription switch 32 , and TRAIP is an E3 ubiquitin-protein ligase 33 . Both genes have been proven to be involved in the prognosis of many cancers 34,35 . Our ndings further revealed that these genes serve as favorable prognostic indicators for survival outcomes in pediatric AML patients, consistent with previous studies.…”

High expression of the TEFM gene predicts poor prognosis in hepatocellular carcinoma

“…In addition, the products of nuclear genes involved in mitochondrial transcription and replication act as communication integrators between nucleus and mitochondria, playing an essential role in both tumorigenesis and homeostase (31,32). Recent studies showed that TEFM acts as a replication-transcription switch which necessary for both replication primer formation and mtDNA transcription elongation, and knockout of TEFM gene also affects RNA processing in human mitochondria (33)(34)(35). To the best of our knowledge, the expression level of TEFM in HCC, the role of TEFM in the occurrence and development of HCC, and its impact on the prognosis of patients with HCC have not been reported yet.…”