Variable copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in advanced gastric cancer patients

Zhang, Guanjun; Qu, Yiping; Dang, Siwen; Yang, Qi; Shi, Bingyin; Hou, Peng

doi:10.1186/1746-1596-8-173

Cited by 56 publications

(64 citation statements)

References 38 publications

(46 reference statements)

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“…After a thorough review of titles and abstracts by two investigators independently, 394 studies were excluded and the full texts of remaining 26 references have also been artificial retrieved for further identification. Finally a total of 20 retrospective studies comprising 5413 patients were included in our study and 18 studies were used for analysis16171819202122252627282930313233343536. Among the included studies for analysis, there were 16 studies recruited Asian patients while 2 studies recruited Caucasian patients.…”

Section: Resultsmentioning

confidence: 99%

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Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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Previous studies have suggested that mitochondrial DNA (mtDNA) copy number was associated with cancer risk. However, no solid conclusion revealed the potential predictive value of mtDNA copy number for cancer prognosis. The present meta-analysis was performed to clarify the problem. Hence, we performed a systematic search in PubMed, EmBase, Web of Science databases independently and a total of eighteen studies comprising 3961 cases satisfied the criteria and finally enrolled. Our results didn’t show the association between them but significant heterogeneity in overall analysis (OS: HR = 0.923, 95% CI: 0.653–1.306, p = 0.652; DFS: HR = 0.997, 95% CI: 0.599–1.659, p = 0.99). However, subgroup analysis stratified by sample came to the opposite conclusion. High level mitochondrial DNA copy number in peripheral blood predicted a poor cancer prognosis (OS: HR = 1.624, 95% CI: 1.211–2.177, p = 0.001; DFS: HR = 1.582, 95% CI: 1.026–2.439, p = 0.038) while patients with high level mitochondrial DNA copy number in tumor tissue exhibited better outcomes (OS: HR = 0.604 95% CI: 0.406–0.899, p = 0.013; DFS: HR = 0.593, 95% CI: 0.411–0.857, p = 0.005). These findings were further proved in detailed analyses in blood or tissue subgroup. In conclusion, our study suggested the elevated mtDNA copy number in peripheral blood predicted a poor cancer prognosis while the better outcome was presented among patients with elevated mtDNA copy number in tumor tissue.

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Section: Resultsmentioning

confidence: 99%

“…Three studies252735 reported mtDNA copy number as three categorical variables and all used middle level of mtDNA copy number as reference. All three studies recruited Asians and measured copy number in tissue.…”

Section: Resultsmentioning

confidence: 99%

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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“…38 An analysis of a different set of patients revealed that increased mtDNA copy number is associated with worse survival in patients with late-stage tumors. 41 In breast cancer, a decrease in mtDNA copy number was correlated with higher histological grade, poorer disease-free survival, and lower overall survival. 42 In colorectal cancer, patients with lower mtDNA copy number showed higher TNM stages and poorer differentiation.…”

Section: Copy Number Changesmentioning

confidence: 99%

Role of mitochondrial dysfunction in cancer progression

Hsu¹,

Tseng

Lee³

2016

Exp Biol Med (Maywood)

221

161

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Deregulated cellular energetics was one of the cancer hallmarks. Several underlying mechanisms of deregulated cellular energetics are associated with mitochondrial dysfunction caused by mitochondrial DNA mutations, mitochondrial enzyme defects, or altered oncogenes/tumor suppressors. In this review, we summarize the current understanding about the role of mitochondrial dysfunction in cancer progression. Point mutations and copy number changes are the two most common mitochondrial DNA alterations in cancers, and mitochondrial dysfunction induced by chemical depletion of mitochondrial DNA or impairment of mitochondrial respiratory chain in cancer cells promotes cancer progression to a chemoresistance or invasive phenotype. Moreover, defects in mitochondrial enzymes, such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase, are associated with both familial and sporadic forms of cancer. Deregulated mitochondrial deacetylase sirtuin 3 might modulate cancer progression by regulating cellular metabolism and oxidative stress. These mitochondrial defects during oncogenesis and tumor progression activate cytosolic signaling pathways that ultimately alter nuclear gene expression, a process called retrograde signaling. Changes in the intracellular level of reactive oxygen species, Ca 2þ , or oncometabolites are important in the mitochondrial retrograde signaling for neoplastic transformation and cancer progression. In addition, altered oncogenes/ tumor suppressors including hypoxia-inducible factor 1 and tumor suppressor p53 regulate mitochondrial respiration and cellular metabolism by modulating the expression of their target genes. We thus suggest that mitochondrial dysfunction plays a critical role in cancer progression and that targeting mitochondrial alterations and mitochondrial retrograde signaling might be a promising strategy for the development of selective anticancer therapy.

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“…Numerous tumors are characterized by an overexpression of uncoupling proteins, for instance, in human colorectal cancers [172–174]. In particular, UCP2 appears to be overexpressed in leukemia and in other forms of cancer [146].…”

Section: Mitochondriamentioning

confidence: 99%

Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

Pacini¹,

Borziani²

2014

IJMS

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Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

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Variable copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in advanced gastric cancer patients

Cited by 56 publications

References 38 publications

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Role of mitochondrial dysfunction in cancer progression

Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

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