Genetic variations of mitochondrial genome modify risk and prognosis of hepatocellular carcinoma patients

Chen, Cheng; Ba, Yanna; Li, Deyang; Du, Xiaohong; Lia, Xin; Yang, Hai; An, Jing; Xing, Jinliang; Yang, Hushan; Dong, Guanglong; Guo, Xu

doi:10.1016/j.clinre.2016.12.002

Cited by 14 publications

(15 citation statements)

References 31 publications

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“…Notably, mitochondrial haplogroups may play roles in common chronic diseases with age, such as the role of the N9a haplogroup in diabetes, the B5 haplogroup involvement in Alzheimer's disease (AD), or the role of G haplogroup in osteoarthritis (Bi et al, 2015;Fang et al, 2016Fang et al, , 2018. Previous studies have found that the mitochondrial M7 haplogroup is predisposed to susceptibility to common chronic diseases such as chronic obstructive pulmonary disease, coronary atherosclerosis, lung cancer, and hepatocellular carcinoma (Sawabe et al, 2011;Zheng et al, 2012a,b;Chen et al, 2017). Notably, evidence has shown that haplogroup M7a is closely associated with Japanese Parkinson's disease (PD).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population

Sun

Yao

et al. 2020

Front. Genet.

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Mitochondrial DNA (mtDNA) haplogroups have been associated with functional impairments (i.e., decreased gait speed and grip strength, frailty), which are risk factors of disability. However, the association between mtDNA haplogroups and ADL disability is still unclear. In this study, we conducted an investigation of 25 mtSNPs defining 17 major mtDNA haplogroups for ADL disability in an aging Chinese population. We found that mtDNA haplogroup M7 was associated with an increased risk of disability (OR = 3.18 [95% CI = 1.29-7.83], P = 0.012). The survival rate of the M7 haplogroup group (6.1%) was lower than that of the non-M7 haplogroup group (9.5%) after a 6-year follow-up. In cellular studies, cytoplasmic hybrid (cybrid) cells with the M7 haplogroup showed distinct mitochondrial functions from the M8 haplogroup. Specifically, the respiratory chain complex capacity was significantly lower in M7 haplogroup cybrids than in M8 haplogroup cybrids. Furthermore, an obvious decreased mitochondrial membrane potential and 40% reduced ATP-linked oxygen consumption were found in M7 haplogroup cybrids compared to M8 haplogroup cybrids. Notably, M7 haplogroup cybrids generated more reactive oxygen species (ROS) than M8 haplogroup cybrids. Therefore, the M7 haplogroup may contribute to the risk of disability via altering mitochondrial function to some extent, leading to decreased oxygen consumption, but increased ROS production, which may activate mitochondrial retrograde signaling pathways to impair cellular and tissue function.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population

Sun

Yao

et al. 2020

Front. Genet.

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“…Viewed from a broader perspective, our results suggest that mtDNA haplogroups may influence the natural history of chronic liver diseases of various etiologies; a notion that is supported by two recent studies. In the first study, the presence of mtDNA haplogroup L was found to exercise a protective effect against the development of non-alcoholic steatohepatitis and pericellular fibrosis in patients with non-alcoholic fatty liver disease [42]; in the second study, carried out in Chinese population with HCC, patients with haplogroup M8 had a lower survival rate than patients with haplogroup D4 [43]. The fact that a large proportion of the participants were treated with interferon could also limit the study’s implications on the natural history of HCV infection.…”

Section: Discussionmentioning

confidence: 99%

European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

et al. 2019

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Background Mitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients. Methods We carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk. Results The study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups ( p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups ( p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values. Conclusions European mitochondrial haplogroups may influence the natural history of chronic hepatitis C. Electronic supplementary material The online version of this article (10.1186/s12967-019-1997-x) contains supplementary material, which is available to authorized users.

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“…As one example, Chen and colleagues used next-generation sequencing to examine the mitochondrial genome of 188 hepatocellular carcinoma (HCC) patients compared with 344 healthy patients to assess associations between mtDNA SNPs (or haplogroups) on patient prognosis (17). The authors identified that haplogroups M7 and M8 had relatively high odds ratios for patients to develop HCC.…”

Section: Mitochondrial Polymorphisms Implicated In Cancermentioning

confidence: 99%

“…The authors identified that haplogroups M7 and M8 had relatively high odds ratios for patients to develop HCC. On the other hand, SNPs T15784C, C16185T, and A16399G were found to be associated with improved prognosis in patients with HCC (17). Another group determined that mtDNA SNP C150T was also important in the prognosis of HCC (18).…”

Section: Mitochondrial Polymorphisms Implicated In Cancermentioning

confidence: 99%

Understanding Mitochondrial Polymorphisms in Cancer

Bussard

Siracusa

2017

Cancer Research

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Alterations in mitochondrial DNA (mtDNA) were once thought to be predominantly innocuous to cell growth. Recent evidence suggests that mtDNA undergo naturally occurring alterations, including mutations and polymorphisms, which profoundly affect the cells in which they appear and contribute to a variety of diseases, including cardiovascular disease, diabetes, and cancer. Furthermore, interplay between mtDNA and nuclear DNA has been found in cancer cells, necessitating consideration of these complex interactions for future studies of cancer mutations and polymorphisms. In this issue of Cancer Research, Vivian and colleagues utilize a unique mouse model, called Mitochondrial Nuclear eXchange mice, that contain the nuclear DNA from one inbred mouse strain, and the mtDNA from a different inbred mouse strain to examine the genomewide nuclear DNA methylation and gene expression patterns of brain tissue. Results demonstrated there were alterations in nuclear DNA expression and DNA methylation driven by mtDNA. These alterations may impact disease pathogenesis. In light of these results, in this review, we highlight alterations in mtDNA, with a specific focus on polymorphisms associated with cancer susceptibility and/or prognosis, mtDNA as cancer biomarkers, and considerations for investigating the role of mtDNA in cancer progression for future studies.

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Genetic variations of mitochondrial genome modify risk and prognosis of hepatocellular carcinoma patients

Cited by 14 publications

References 31 publications

Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population

Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population

European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

Understanding Mitochondrial Polymorphisms in Cancer

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