Circulating mitochondria DNA, a non-invasive cancer diagnostic biomarker candidate

Afrifa, Justice; Zhao, Tai-Yun; Yu, Jingcui

doi:10.1016/j.mito.2018.12.003

Cited by 38 publications

(27 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biomarkers are molecular signatures and indicators of normal biological and pathological process, and thus may provide useful information for the detection, diagnosis, and prognosis of disease. Many studies have attempted to identify cancer biomarkers in non-invasive samples [1][2][3][4]. Saliva has direct contact with OSCC lesions, which gives it particular potential as a specific and sensitive screening tool.…”

Section: Introductionmentioning

confidence: 99%

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

Kang

et al. 2020

JCM

View full text Add to dashboard Cite

We evaluated potential biomarkers in human whole saliva for the early diagnosis of oral squamous cell carcinoma (OSCC). We selected 30 candidate genes with relevance to cancer from recent reports in PubMed. Saliva samples were obtained from 34 non-tumor control and 33 OSCC patients. Real-time PCR was performed, and mRNA levels were compared. Normalized mRNA levels of six genes (NGFI-A binding protein 2 (NAB2), cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1), nuclear pore complex interacting protein family, member B4 (NPIPB4), monoamine oxidase B (MAOB), sialic acid acetyltransferase (SIAE), and collagen, type III, alpha 1 (COL3A1)) were significantly lower in saliva of OSCC patients. Receiver operating characteristics (ROC) analysis was used to individually evaluate the predictive power of the potential biomarkers for OSCC diagnosis. The area under the curve (AUC) values were evaluated for the OSCC vs. non-tumor groups via univariate ROC analyses, as well as multivariate ROC analyses of combinations of multiple potential biomarkers. The combination of CYP27A1 + SIAE showed a favorable AUC value of 0.84. When we divided saliva samples into two groups according to age using a 60-year cut-off, with OSCC patients and controls evaluated together, the AUC of MAOB–NAB2 was more predictive of OSCC in the under-60 group (AUC, 0.91; sensitivity, 0.92; and specificity, 0.86) than any other gene combination. These results are expected to aid the early diagnosis of OSCC, especially in patients under 60 years of age. While more studies with larger numbers of patients are necessary, our result suggest that salivary mRNA would be a potent biomarker for early OSCC diagnosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

Kang

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…4 In recent years, the mtDNA content has been widely utilized as a biomarker of mitochondrial function and is being used increasingly to study disease-associated changes in blood samples and other body fluids from large population. [5][6][7] Cellular mtDNA, contained within the mitochondria, encodes essential components of the electron transport chain, crucial for the oxidative phosphorylation process by which cells derive most of their energy in the form of ATP. 8,9 The cellular mtDNA content of a particular cell or tissue usually correlates with its bioenergetic potential and is considered indicative of mitochondrial mass.…”

mentioning

confidence: 99%

“…Due to its resemblance to bacterial genomes, this cell-free (cf) mtDNA can activate the TLR-9 pathway, leading to activation of TNF-alpha and a downstream inflammatory response. [11][12][13] Peripheral blood is frequently used for investigation of the mtDNA content due to ease of collection, processing, and storage, with hundreds of studies reporting disease-associated changes 7,14,15 ; however, current methods do not allow differentiation between cellular or cell-free (cf) mtDNA. The cellular fraction of whole blood contains erythrocytes, platelets, and several types of white blood cells, including peripheral blood mononuclear cells (PBMCs) and granulocytes.…”

mentioning

confidence: 99%

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

et al. 2020

View full text Add to dashboard Cite

Circulating mitochondrial DNA (mtDNA), widely studied as a disease biomarker, comprises of mtDNA located within mitochondria, indicative of mitochondrial function, and cell‐free (cf) mtDNA linked to inflammation. The purpose of this study was to determine the ranges of, and relationship between, cellular and cf mtDNA in human blood. Whole blood from 23 controls (HC) and 20 patients with diabetes was separated into peripheral blood mononuclear cells (PBMCs), plasma, and serum. Total DNA was isolated and mtDNA copy numbers were determined using absolute quantification. Cellular mtDNA content in PBMCs was higher than in peripheral blood and a surprisingly high level of cf mtDNA was present in serum and plasma of HC, with no direct relationship between cellular and cf mtDNA content within individuals. Diabetes patients had similar levels of cellular mtDNA compared to healthy participants but a significantly higher cf mtDNA content. Furthermore, only in patients with diabetes, we observed a correlation between whole blood and plasma mtDNA levels, indicating that the relationship between cellular and cf mtDNA content is affected by disease status. In conclusion, when evaluating mtDNA in human blood as a biomarker of mitochondrial dysfunction, it is important to measure both cellular and cf mtDNA.

show abstract

“…Cellular coordination of mtDNA content is a dynamic and tightly regulated process (Li et al 2005;Scarpulla 2006;Wu et al 2006); however, the mechanisms by which mtDNA copy number is monitored and controlled are not well understood (Moraes 2001;Clay Montier et al 2009;Klingbeil and Shapiro 2009). In addition, alterations in mtDNA levels often accompany key pathophysiological changes during the transition from healthy to diseased states (Butow and Avadhani 2004), and a number of age-related diseases correlate with mtDNA abundance, including cardiovascular disease (Yue et al 2018), type 2 diabetes (Malik et al 2009;Monickaraj et al 2012), cancer (Afrifa et al 2018), and dementia (Rice et al 2014;Pyle et al 2016). Furthermore, mtDNA levels in peripheral blood mononuclear cells (PBMCs) gradually decrease during aging and are associated with health status among the elderly (Mengel-From et al 2014;Wachsmuth et al 2016), suggesting that mtDNA may be a biomarker of biological (not chronological) age and disease exposure (Pieters et al 2015;Qiu et al 2015;Tyrka et al 2015).…”

mentioning

confidence: 99%

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution

et al. 2019

View full text Add to dashboard Cite

Mitochondria are involved in a number of diverse cellular functions, including energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, and motility, as well as free radical generation. Mitochondrial DNA (mtDNA) is present at hundreds to thousands of copies per cell in a tissue-specific manner. mtDNA copy number also varies during aging and disease progression and therefore might be considered as a biomarker that mirrors alterations within the human body. Here, we present a new quantitative, highly sensitive droplet digital PCR (ddPCR) method, droplet digital mitochondrial DNA measurement (ddMDM), to measure mtDNA copy number not only from cell populations but also from single cells. Our developed assay can generate data in as little as 3 h, is optimized for 96-well plates, and also allows the direct use of cell lysates without the need for DNA purification or nuclear reference genes. We show that ddMDM is able to detect differences between samples whose mtDNA copy number was close enough as to be indistinguishable by other commonly used mtDNA quantitation methods. By utilizing ddMDM, we show quantitative changes in mtDNA content per cell across a wide variety of physiological contexts including cancer progression, cell cycle progression, human T cell activation, and human aging.

show abstract

Circulating mitochondria DNA, a non-invasive cancer diagnostic biomarker candidate

Cited by 38 publications

References 67 publications

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

A case for measuring both cellular and cell‐free mitochondrial DNA as a disease biomarker in human blood

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution

Contact Info

Product

Resources

About