Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

Stawski, Robert; Stec-Martyna, Emilia; Chmielecki, Adam; Nowak, Dariusz; Perdas, Ewelina

doi:10.3390/biology10090906

Cited by 17 publications

(17 citation statements)

References 51 publications

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“…To sum up, cell-free DNA is a marker with a wide spectrum of applications, successfully applied for many different diseases. Moreover, it is also characterized by a much higher sensitivity than standard biochemical markers [4,127]. To this end, cfDNA tests can be greatly improved by adding a combination with several standard diagnostic biochemical biomarkers to them.…”

Section: Discussionmentioning

confidence: 99%

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management

Stawski

Nowak

Perdas

2022

Viruses

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WHO has declared COVID-19 as a worldwide, public health emergency. The elderly, pregnant women, and people with associated co-morbidities, including pulmonary disease, heart failure, diabetes, and cancer are the most predisposed population groups to infection. Cell-free DNA is a very commonly applied marker, which is elevated in various pathological conditions. However, it has a much higher sensitivity than standard biochemical markers. cfDNA appears to be an effective marker of COVID-19 complications, and also serves as a marker of certain underlying health conditions and risk factors of severe illness during COVID-19 infection. We aimed to present the possible mechanisms and sources of cfDNA released during moderate and severe infections. Moreover, we attempt to verify how efficiently cfDNA increase could be applied in COVID-19 risk assessment and how it corresponds with epidemiological data.

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Section: Discussionmentioning

confidence: 99%

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management

Stawski

Nowak

Perdas

2022

Viruses

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“…In organ transplantation, the diagnostic role of cfDNA has been extensively studied in heart, kidney, and lung transplantations [ 96 ]. However, only one study exists on this topic in liver transplantation [ 97 ].…”

Section: Cell-free Dna As a Molecular Marker Or A Diagnostic Toolmentioning

confidence: 99%

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

Műzes¹,

Barta²,

Szabó³

et al. 2022

Biomedicines

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The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. However, extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, such as autoimmune disorders and malignancies, which has sparked interest in using cfDNA as a possible biomarker. In recent years, the widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research. The majority of studies have mainly focused on the function of cfDNA as a biomarker. However, research regarding the immunological consequences of cfDNA, such as its potential immunomodulatory or therapeutic benefits, is still in its infancy. This article discusses the involvement of various DNA-sensing receptors (e.g., absent in melanoma-2; Toll-like receptor 9; cyclic GMP–AMP synthase/activator of interferon genes) in identifying host cfDNA as a potent danger-associated molecular pattern. Furthermore, we aim to summarize the results of the experimental studies that we recently performed and highlight the immunomodulatory capacity of cfDNA, and thus, the potential for possible therapeutic consideration.

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“…This could usefully complement the current NGS-based metagenomic approaches to bacterial DNA detection in plasma with significantly improved sensitivity and turnaround time [35,36]. Recent reviews have indicated a growing interest in cfDNA application in cancer and non-cancer studies including sepsis [50], as well as its utility in predicting complicated COVID-19 [51].…”

Section: Stratification Of Bacteraemic Subjectsmentioning

confidence: 99%

Plasma cfDNA predictors of established bacteraemic infection

Urosevic

Merritt

Inglis

2022

Access Microbiology

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Introduction. Increased plasma cell-free DNA (cfDNA) has been reported for various diseases in which cell death and tissue/organ damage contribute to pathogenesis, including sepsis. Gap Statement. While several studies report a rise in plasma cfDNA in bacteraemia and sepsis, the main source of cfDNA has not been identified. Aim. In this study, we wanted to determine which of nuclear, mitochondrial or bacterial cfDNA is the major contributor to raised plasma cfDNA in hospital subjects with bloodstream infections and could therefore serve as a predictor of bacteraemic disease severity. Methodology. The total plasma concentration of double-stranded cfDNA was determined using a fluorometric assay. The presence of bacterial DNA was identified by PCR and DNA sequencing. The copy numbers of human genes, nuclear β globin and mitochondrial MTATP8, were determined by droplet digital PCR. The presence, size and concentration of apoptotic DNA from human cells were established using lab-on-a-chip technology. Results. We observed a significant difference in total plasma cfDNA from a median of 75 ng ml−1 in hospitalised subjects without bacteraemia to a median of 370 ng ml−1 (P=0.0003) in bacteraemic subjects. The copy numbers of nuclear DNA in bacteraemic also differed between a median of 1.6 copies µl−1 and 7.3 copies µl−1 (P=0.0004), respectively. In contrast, increased mitochondrial cfDNA was not specific for bacteraemic subjects, as shown by median values of 58 copies µl−1 in bacteraemic subjects, 55 copies µl−1 in other hospitalised subjects and 5.4 copies µl−1 in healthy controls. Apoptotic nucleosomal cfDNA was detected only in a subpopulation of bacteraemic subjects with documented comorbidities, consistent with elevated plasma C-reactive protein (CRP) levels in these subjects. No bacterial cfDNA was reliably detected by PCR in plasma of bacteraemic subjects over the course of infection with several bacterial pathogens. Conclusions. Our data revealed distinctive plasma cfDNA signatures in different groups of hospital subjects. The total cfDNA was significantly increased in hospital subjects with laboratory-confirmed bloodstream infections comprising nuclear and apoptotic, but not mitochondrial or bacterial cfDNAs. The apoptotic cfDNA, potentially derived from blood cells, predicted established bacteraemia. These findings deserve further investigation in different hospital settings, where cfDNA measurement could provide simple and quantifiable parameters for monitoring a disease progression.

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Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

Cited by 17 publications

References 51 publications

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

Plasma cfDNA predictors of established bacteraemic infection

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