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

Zai-Yi Fei; Wei-Si Wang; Su-Fen Li; Jia-Ji Zi; Li Yang; Ting Liu; Song Ao; Qian-Qian Liu; Qing-Hua Cui; Min Yu; Wei Xiong

doi:10.21037/jgo-20-120

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

J Gastrointest Oncol. 2020 Dec;11(6):1291-1304. doi: 10.21037/jgo-20-120.

Authors

Zai-Yi Fei^{1

2}, Wei-Si Wang^{3

4}, Su-Fen Li^{3

4}, Jia-Ji Zi³, Li Yang^{1

2}, Ting Liu^{1

2}, Song Ao^{1

2}, Qian-Qian Liu^{1

2}, Qing-Hua Cui^{1

2}, Min Yu^{1

2}, Wei Xiong^{3

4}

Affiliations

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.

Keywords: Mitochondrial transcription elongation factor (TEFM); TCGA dataset; hepatocellular carcinoma (HCC); immunohistochemistry; prognosis.