Impact of an MT-RNR1 Gene Polymorphism on Hepatocellular Carcinoma Progression and Clinical Characteristics

Mitochondrial DNA (mtDNA) mutations are highly associated with cancer progression. The poor prognosis of hepatocellular carcinoma (HCC) is largely due to high rates of tumor metastasis. This emphasizes the urgency of identifying these patients in advance and developing new therapeutic targets for su...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-01, Vol.22 (3), p.1119
Main Authors: Lin, Yang-Hsiang, Chu, Yu-De, Lim, Siew-Na, Chen, Chun-Wei, Yeh, Chau-Ting, Lin, Wey-Ran
Format: Article
Language:English
Subjects:
Alcoholism
Aspartate transaminase
Cirrhosis
Deoxyribonucleic acid
DNA
Gene polymorphism
Genes
Genomes
Hepatocellular carcinoma
Hepatoma
Hexokinase
Histology
Liver cancer
Liver cirrhosis
Medical prognosis
Metabolism
Metastases
Metastasis
Mitochondrial DNA
Multivariate analysis
Mutation
Polymorphism
Prognosis
Prostate cancer
Proteins
Risk analysis
Risk factors
rRNA 12S
Subgroups
Survival
Transaminase
Tumors
α-Fetoprotein
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Summary:Mitochondrial DNA (mtDNA) mutations are highly associated with cancer progression. The poor prognosis of hepatocellular carcinoma (HCC) is largely due to high rates of tumor metastasis. This emphasizes the urgency of identifying these patients in advance and developing new therapeutic targets for successful intervention. However, the issue of whether mtDNA influences tumor metastasis in hepatoma remains unclear. In the current study, multiple mutations in mtDNA were identified by sequencing HCC samples. Among these mutations, mitochondrially encoded 12S rRNA (MT-RNR1) G709A was identified as a novel potential candidate. The MT-RNR1 G709A polymorphism was an independent risk factor for overall survival and distant metastasis-free survival. Subgroup analysis showed that in patients with cirrhosis, HBV-related HCC, α-fetoprotein ≥ 400 ng/mL, aspartate transaminase ≥ 31 IU/L, tumor number > 1, tumor size ≥ 5 cm, and histology grade 3-4, MT-RNR1 G709A was associated with both shorter overall survival and distant metastasis-free survival. Mechanistically, MT-RNR1 G709A was clearly associated with hexokinase 2 (HK2) expression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel associations among MT-RNR1 G709A and HK2 are an important risk factor in HCC patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22031119