Zai-Yi Fei1,2, Wei-Si Wang3,4, Su-Fen Li3,4, Jia-Ji Zi3, Li Yang1,2, Ting Liu1,2, Song Ao1,2, Qian-Qian Liu1,2, Qing-Hua Cui1,2, Min Yu1,2, Wei Xiong3,4. 1. School of Life Sciences, Yunnan University, Kunming, China. 2. Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Yunnan University, Kunming, China. 3. College of Basic Medical Sciences, Dali University, Dali, China. 4. Key Laboratory for Clinical Biochemistry of High Education in Yunnan Province, Dali University, Dali, China.
Abstract
BACKGROUND: 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. METHODS: 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 TEFM 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. RESULTS: 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). CONCLUSIONS: 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. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: 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. METHODS: 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 TEFM 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. RESULTS: 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). CONCLUSIONS: 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. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Mukesh Verma; Robert K Naviaux; Masashi Tanaka; Deepak Kumar; Claudio Franceschi; Keshav K Singh Journal: Cancer Res Date: 2007-01-09 Impact factor: 12.701
Authors: Young Seok Ju; Ludmil B Alexandrov; Moritz Gerstung; Inigo Martincorena; Serena Nik-Zainal; Manasa Ramakrishna; Helen R Davies; Elli Papaemmanuil; Gunes Gundem; Adam Shlien; Niccolo Bolli; Sam Behjati; Patrick S Tarpey; Jyoti Nangalia; Charles E Massie; Adam P Butler; Jon W Teague; George S Vassiliou; Anthony R Green; Ming-Qing Du; Ashwin Unnikrishnan; John E Pimanda; Bin Tean Teh; Nikhil Munshi; Mel Greaves; Paresh Vyas; Adel K El-Naggar; Tom Santarius; V Peter Collins; Richard Grundy; Jack A Taylor; D Neil Hayes; David Malkin; Christopher S Foster; Anne Y Warren; Hayley C Whitaker; Daniel Brewer; Rosalind Eeles; Colin Cooper; David Neal; Tapio Visakorpi; William B Isaacs; G Steven Bova; Adrienne M Flanagan; P Andrew Futreal; Andy G Lynch; Patrick F Chinnery; Ultan McDermott; Michael R Stratton; Peter J Campbell Journal: Elife Date: 2014-10-01 Impact factor: 8.140