Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers

Yu, Man

doi:10.1016/j.lfs.2011.05.010

Cited by 178 publications

(168 citation statements)

References 79 publications

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“…Our data are consistent with previous studies showing that ccf‐mtDNA levels are elevated in a variety of diseases, such as myocardial infarction8, major trauma2, sepsis12, malignancy13, 14 and intensive care unit conditions15. The present study also showed that mtDNA can be used to discriminate CHD patients with DM from non‐CHD‐DM, although the ability of mtDNA to discriminate CHD patients with DM from those without DM was decreased, suggesting mtDNA is a biomarker for CHD with DM.…”

Section: Discussionsupporting

confidence: 93%

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Liu

Zou

Tang

et al. 2015

J of Diabetes Invest

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Aims/IntroductionCirculating cell‐free mitochondrial deoxyribonucleic acid (ccf‐mtDNA) is presumably derived from injured tissues or cells in the body and has been suggested to be potential biomarker in several diseases. The present study explored whether mtDNA could be used as a biomarker to evaluate disease in coronary heart disease (CHD) patients with or without diabetes mellitus (DM).Materials and MethodsA total of 50 CHD patients with type 2 diabetes, 50 CHD patients without type 2 diabetes, and 50 age‐ and sex‐matched patients without CHD and DM (non‐CHD‐DM) were recruited. Ccf‐mtDNA levels were assessed by measuring the nicotinamide adenine dinucleotide dehydrogenase 1 gene using quantitative real‐time polymerase chain reaction. Receiver operating characteristic curve analysis of plasma mtDNA in CHD with or without DM was also determined. Multivariate logistic regression analyses were carried out to determine the correlation between the mtDNA levels and traditional CHD risk factors.ResultsThe plasma ccf‐mtDNA levels were significantly elevated in CHD patients with DM compared with those without and non‐CHD‐DM. The area under the receiver operating characteristic curves of mtDNA in CHD patients with DM vs non‐CHD‐DM was 0.907%. Correlation analyses of the mtDNA levels and traditional CHD risk factors showed that the mtDNA levels were significantly correlated with fasting blood glucose in CHD patients with DM.ConclusionsCcf‐mtDNA levels can be used as a biomarker in CHD patients with DM.

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Section: Discussionsupporting

confidence: 93%

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Liu

Zou

Tang

et al. 2015

J of Diabetes Invest

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“…Due in part to these advantages over nDNA-based methods, the detection of aberrant changes in mtDNA brings a lot attention for its usage in the early diagnosis of cancer. In light of the promise of using circulating DNA as a non-invasive marker for cancer assessment, changes in blood mtDNA may serve as a particularly sensitive, early biomarker for the non-invasive detection of tumors (Fliss et al, 2000;Radpour et al, 2009;Yu, 2011;GonzalezMasia et al, 2013). Mutated mtDNA is readily detected in the tissue of many solid tumors (Copeland et al, 2002) as well as bodily fluids sampled in early-stage patients (Hibi et al, 2001;Jeronimo et al, 2001;Nomoto et al, 2002;Okochi et al, 2002;Yu, 2011).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

Xia

Wang²,

Geng³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer. Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves. Results: The mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage. Conclusions: The mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.

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“…Since one cancer cell can be polyploidy, one mitochondrion may be polyploidy as well when it goes abnormal, which in turn makes it even more uncertain how an mtDNA mutation contributes to IR in individual patients (but no in individual cell lines). Regardless what answers for these questions may be, mitochondrial alterations are impermanent since exercise and oxidative prods can induce mitochondrial biogenesis [21,22], and since the number of mitochondria may be increased in some cancer cells [23,24]. Besides mitochondria, many abnormalities seen in T2D are also ascribed to abnormal cellular RNAs, proteins, lipids, etc, such as changed phosphorylation [25] or conformation of proteins [26][27][28].…”

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confidence: 99%

Is Type 2 Diabetes One of Such Aging Phenomena That Lack an Irreversible Structural Change?

Jia¹,

Chen²,

Jia³

et al. 2015

J Diabetes Metab

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All biological functions should have a structural basis. Any functional change should be due to an alteration in the related structure. If a functional change is irreversible, it should be due to the irreversibility of the structural alteration. For instance, cancer is irreversible because cancer cells have irreversible genetic mutations. However, Type 2 Diabetes (T2D) with Insulin-Resistance (IR) as a central mechanism is irreversible but seems to lack a corresponding irreversible structural change. IR and T2D exhibit many abnormalities that are attributable to altered mitochondria or altered cellular RNAs, proteins, lipids, etc. without genetic mutations involved. These alterations are reversible, because mitochondrial biogenesis can be induced by such as exercise whereas RNAs, proteins and lipids will degrade after some time. Aging is irreversible but many aging manifestations also lack corresponding permanent structural changes, and IR may be one such manifestation. IR affects mainly striated muscles, adipose tissue, brain and liver that are collectively defined herein as the "catabolic cell type" for their low proliferation rates but high metabolism of glucose via oxidation-phosphorylation in mitochondria. In contrast, fast-proliferating cells are defined as the "anabolic cell type" because they are the main cancer origins and often metabolize glucose via glycolysis. Dichotomizing T2D-and cancer-targeted cells and pointing out that the irreversible IR as an aging phenomenon lacks a corresponding irreversible structural change may help understand the differences between, and the mechanisms of, T2D and cancer, although these concepts challenge the "structural-functional relationship" dogma in not only biology but also philosophy. We have been Taught that a Function is Based on a StructureWe as biologists or medical researchers are well educated on structures of various organisms, including the human one. Here, a structure can be something fairly large, such as the anatomy at the macroscopic and microscopic levels, but can also be something very small at the molecular level, such as the sequences and conformations of the DNAs, RNAs, proteins, lipids, starches, etc. Out of this educational background, a concept of structural-functional relationship has been firmly entrenched in our mind. This concept says that a function is based on one sort of architecture or makeup, and any change in a function ultimately can be causally linked to an alteration in the related structure. If the structural alteration is reversed, the function will return to normal as well. For example, based on this rationale, cardiac surgery is performed to fix congenital heart malformation of children. Conversely, irreversible change in a function should be due to an irreversible alteration of a structure.At the molecular level, for a long time it had been thought that proteins were the only executors of cellular functions and all genes had to be expressed ultimately as proteins to be functional, but we now know that many RNAs can al...

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Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers

Cited by 178 publications

References 79 publications

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

Is Type 2 Diabetes One of Such Aging Phenomena That Lack an Irreversible Structural Change?

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