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Special Issue "Cell-Free Nucleic Acids"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2019).

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A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Bálint Nagy
Website SciProfiles
Guest Editor
Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Interests: comparison of nucleic acid isolation methods; cell-free nucleic acid isolation; gene expression measurement; clinical application of liquid biopsy; diagnosis of genetic diseases; cell-free gDNA; mtDNA; miRNA and lncRNA studies in oncological and cardiovascular diseases; exosome isolation methods; nucleic acid measurements from exosomes
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Liquid biopsy has recently become a very popular sampling procedure. The main advantage of this method is the possibility of easy cell-free nucleic acids isolation from different bloody fluids and their use in diagnostic or screening processes. The other advantage is the possibility to follow up patients’ treatments. Liquid biopsy is applicable during the diagnosis of oncological, cardiovascular, and infectious diseases. Gene expression studies on gDNA, mtDNA, miRNA, and lncRNA could give valuable information to researchers and clinicians. Currently, it is very popular to obtain exosomes from liquid biopsies and use them in similar studies. Understanding their role in different pathological conditions could give us valuable information on cell-cell-tissue communication. The identification of new extra- and intracellular signaling nucleic acid molecules and pathways could help in the diagnosis and treatment of patients.

Cell-free DNAs are widely used in the prenatal detection of genetic diseases. Recently oncological diseases are the focus of research and the newest area is the cardiovascular diseases.

Therefore, authors are invited to submit original research and review articles which address the progress and current standing of cell-free nucleic acids.

Topics include, but are not limited to:

  • Gene expression studies in different diseases using cell-free nucleic acids;
  • Use of cell-free nucleic acids as biomarkers in different diseases;
  • Techniques for isolation, detection, analysis, and identification of signaling nucleic acid molecules, pathways, and networks.

Prof. Bálint Nagy
Guest Editor

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Keywords

  • Cell-free nucleic acids
  • Liquid biopsy
  • Gene expression
  • Prenatal diagnosis
  • Oncology
  • Cardiovascular diseases
  • Exosomes

Published Papers (14 papers)

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Editorial

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Open AccessEditorial
Cell-Free Nucleic Acids
Int. J. Mol. Sci. 2019, 20(22), 5645; https://doi.org/10.3390/ijms20225645 - 12 Nov 2019
Cited by 1
Abstract
The discovery of cell-free DNA (cfDNA) dates back to 1948, when Mandel and Metais found it in the sera of cancer patients [...] Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available

Research

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Open AccessArticle
Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients
Int. J. Mol. Sci. 2019, 20(18), 4533; https://doi.org/10.3390/ijms20184533 - 13 Sep 2019
Cited by 8
Abstract
Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the [...] Read more.
Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein–protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessCommunication
Identification of Structural Variation from NGS-Based Non-Invasive Prenatal Testing
Int. J. Mol. Sci. 2019, 20(18), 4403; https://doi.org/10.3390/ijms20184403 - 07 Sep 2019
Cited by 3
Abstract
Copy number variants (CNVs) are an important type of human genome variation, which play a significant role in evolution contribute to population diversity and human genetic diseases. In recent years, next generation sequencing has become a valuable tool for clinical diagnostics and to [...] Read more.
Copy number variants (CNVs) are an important type of human genome variation, which play a significant role in evolution contribute to population diversity and human genetic diseases. In recent years, next generation sequencing has become a valuable tool for clinical diagnostics and to provide sensitive and accurate approaches for detecting CNVs. In our previous work, we described a non-invasive prenatal test (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA for detection of CNV aberrations ≥600 kbp. We reanalyzed NIPT genomic data from 5018 patients to evaluate CNV aberrations in the Slovak population. Our analysis of autosomal chromosomes identified 225 maternal CNVs (47 deletions; 178 duplications) ranging from 600 to 7820 kbp. According to the ClinVar database, 137 CNVs (60.89%) were fully overlapping with previously annotated variants, 66 CNVs (29.33%) were in partial overlap, and 22 CNVs (9.78%) did not overlap with any previously described variant. Identified variants were further classified with the AnnotSV method. In summary, we identified 129 likely benign variants, 13 variants of uncertain significance, and 83 likely pathogenic variants. In this study, we use NIPT as a valuable source of population specific data. Our results suggest the utility of genomic data from commercial CNV analysis test as background for a population study. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessCommunication
Sex, Age, and Bodyweight as Determinants of Extracellular DNA in the Plasma of Mice: A Cross-Sectional Study
Int. J. Mol. Sci. 2019, 20(17), 4163; https://doi.org/10.3390/ijms20174163 - 26 Aug 2019
Cited by 2
Abstract
Extracellular DNA (ecDNA) is studied as a possible biomarker, but also as a trigger of the immune responses important for the pathogenesis of several diseases. Extracellular deoxyribonuclease (DNase) activity cleaves ecDNA. The aim of our study was to describe the interindividual variability of [...] Read more.
Extracellular DNA (ecDNA) is studied as a possible biomarker, but also as a trigger of the immune responses important for the pathogenesis of several diseases. Extracellular deoxyribonuclease (DNase) activity cleaves ecDNA. The aim of our study was to describe the interindividual variability of ecDNA and DNase activity in the plasma of healthy mice, and to analyze the potential determinants of the variability, including sex, age, and bodyweight. In this experiment, 58 adult CD1 mice (41 females and 31 males) of a variable age (3 to 16 months old) and bodyweight (females 25.7 to 52.1 g, males 24.6 to 49.6 g) were used. The plasma ecDNA was measured using a fluorometric method. The nuclear ecDNA and mitochondrial ecDNA were quantified using real-time PCR. The deoxyribonuclease activity was assessed using the single radial enzyme diffusion method. The coefficient of variance for plasma ecDNA was 139%, and for DNase 48%. Sex differences were not found in the plasma ecDNA (52.7 ± 73.0 ηg/mL), but in the DNase activity (74.5 ± 33.5 K.u./mL for males, and 47.0 ± 15.4 K.u./mL for females). There were no associations between plasma ecDNA and bodyweight or the age of mice. Our study shows that the variability of plasma ecDNA and DNase in adult healthy mice is very high. Sex, age, and bodyweight seem not to be major determinants of ecDNA variability in healthy mice. As ecDNA gains importance in the research of several diseases, it is of importance to understand its production and cleavage. Further studies should, thus, test other potential determinants, taking into account cleavage mechanisms other than DNase. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessArticle
Aberrant Methylation Status of Tumour Suppressor Genes in Ovarian Cancer Tissue and Paired Plasma Samples
Int. J. Mol. Sci. 2019, 20(17), 4119; https://doi.org/10.3390/ijms20174119 - 23 Aug 2019
Cited by 2
Abstract
Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis [...] Read more.
Ovarian cancer is a highly heterogeneous disease and its formation is affected by many epidemiological factors. It has typical lack of early signs and symptoms, and almost 70% of ovarian cancers are diagnosed in advanced stages. Robust, early and non-invasive ovarian cancer diagnosis will certainly be beneficial. Herein we analysed the regulatory sequence methylation profiles of the RASSF1, PTEN, CDH1 and PAX1 tumour suppressor genes by pyrosequencing in healthy, benign and malignant ovarian tissues, and corresponding plasma samples. We recorded statistically significant higher methylation levels (p < 0.05) in the CDH1 and PAX1 genes in malignant tissues than in controls (39.06 ± 18.78 versus 24.22 ± 6.93; 13.55 ± 10.65 versus 5.73 ± 2.19). Higher values in the CDH1 gene were also found in plasma samples (22.25 ± 14.13 versus 46.42 ± 20.91). A similar methylation pattern with positive correlation between plasma and benign lesions was noted in the CDH1 gene (r = 0.886, p = 0.019) and malignant lesions in the PAX1 gene (r = 0.771, p < 0.001). The random forest algorithm combining methylation indices of all four genes and age determined 0.932 AUC (area under the receiver operating characteristic (ROC) curve) prediction power in the model classifying malignant lesions and controls. Our study results indicate the effects of methylation changes in ovarian cancer development and suggest that the CDH1 gene is a potential candidate for non-invasive diagnosis of ovarian cancer. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessArticle
Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing
Int. J. Mol. Sci. 2019, 20(16), 3959; https://doi.org/10.3390/ijms20163959 - 14 Aug 2019
Cited by 3
Abstract
The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources [...] Read more.
The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessArticle
Adaptable Model Parameters in Non-Invasive Prenatal Testing Lead to More Stable Predictions
Int. J. Mol. Sci. 2019, 20(14), 3414; https://doi.org/10.3390/ijms20143414 - 11 Jul 2019
Cited by 1
Abstract
Recent advances in massively parallel shotgun sequencing opened up new options for affordable non-invasive prenatal testing (NIPT) for fetus aneuploidy from DNA material extracted from maternal plasma. Tests typically compare chromosomal distributions of a tested sample with a control set of healthy samples [...] Read more.
Recent advances in massively parallel shotgun sequencing opened up new options for affordable non-invasive prenatal testing (NIPT) for fetus aneuploidy from DNA material extracted from maternal plasma. Tests typically compare chromosomal distributions of a tested sample with a control set of healthy samples with unaffected fetuses. Deviations above certain threshold levels are concluded as positive findings. The main problem with this approach is that the variance of the control set is dependent on the number of sequenced fragments. The higher the amount, the more precise the estimation of actual chromosomal proportions is. Testing a sample with a highly different number of sequenced reads as used in training may thus lead to over- or under-estimation of their variance, and so lead to false predictions. We propose the calculation of a variance for each tested sample adaptively, based on the actual number of its sequenced fragments. We demonstrate how it leads to more stable predictions, mainly in real-world diagnostics with the highly divergent inter-sample coverage. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessArticle
The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs
Int. J. Mol. Sci. 2019, 20(12), 2972; https://doi.org/10.3390/ijms20122972 - 18 Jun 2019
Cited by 12
Abstract
The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation [...] Read more.
The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation and if this differentiation would lead to the improvement of the diagnostical potential. The retrospective study on singleton Caucasian pregnancies was performed within 6/2011-2/2019. The case control study, nested in a cohort, involved women that later developed GH (n = 57), PE (n = 43), FGR (n = 63), and 102 controls. Maternal plasma exosome profiling was performed with the selection of C19MC microRNAs with diagnostical potential only (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) using real-time RT-PCR. The down-regulation of miR-517-5p, miR-520a-5p, and miR-525-5p was observed in patients with later occurrence of GH and PE. Maternal plasma exosomal profiling of selected C19MC microRNAs also revealed a novel down-regulated biomarker during the first trimester of gestation (miR-520a-5p) for women destinated to develop FGR. First trimester circulating plasma exosomes possess the identical C19MC microRNA expression profile as placental tissues derived from patients with GH, PE and FGR after labor. The predictive accuracy of first trimester C19MC microRNA screening (miR-517-5p, miR-520a-5p, and miR-525-5p) for the diagnosis of GH and PE was significantly higher in the case of expression profiling of maternal plasma exosomes compared to expression profiling of the whole maternal plasma samples. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessArticle
Cell-Free, Embryo-Specific sncRNA as a Molecular Biological Bridge between Patient Fertility and IVF Efficiency
Int. J. Mol. Sci. 2019, 20(12), 2912; https://doi.org/10.3390/ijms20122912 - 14 Jun 2019
Cited by 3
Abstract
Small noncoding RNAs (sncRNAs) are key regulators of the majority of human reproduction events. Understanding their function in the context of gametogenesis and embryogenesis will allow insight into the possible causes of in vitro fertilization (IVF) implantation failure. The aim of this study [...] Read more.
Small noncoding RNAs (sncRNAs) are key regulators of the majority of human reproduction events. Understanding their function in the context of gametogenesis and embryogenesis will allow insight into the possible causes of in vitro fertilization (IVF) implantation failure. The aim of this study was to analyze the sncRNA expression profile of the spent culture media on day 4 after fertilization and to reveal a relationship with the morphofunctional characteristics of gametes and resultant embryos, in particular, with the embryo development and implantation potential. Thereto, cell-free, embryo-specific sncRNAs were identified by next generation sequencing (NGS) and quantified by reverse transcription coupled with polymerase chain reaction (RT-PCR) in real-time. Significant differences in the expression level of let-7b-5p, let-7i-5p, piR020401, piR16735, piR19675, piR20326, and piR17716 were revealed between embryo groups of various morphological gradings. Statistically significant correlations were found between the expression profiles of piR16735 and piR020401 with the oocyte-cumulus complex number, let-7b-5p and piR020401 with metaphase II oocyte and two pronuclei embryo numbers, let-7i-5p and piR20497 with the spermatozoid count per milliliter of ejaculate, piR19675 with the percentage of linearly motile spermatozoids, let-7b-5p with the embryo development grade, and let-7i-5p with embryo implantation. According to partial least squares discriminant analysis (PLS-DA), the expression levels of let-7i-5p (Variable Importance in Projection score (VIP) = 1.6262), piR020401 (VIP = 1.45281), and piR20497 (VIP = 1.42765) have the strongest influences on the implantation outcome. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Review

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Open AccessReview
Current Trends in Applications of Circulatory Microchimerism Detection in Transplantation
Int. J. Mol. Sci. 2019, 20(18), 4450; https://doi.org/10.3390/ijms20184450 - 10 Sep 2019
Cited by 3
Abstract
Primarily due to recent advances of detection techniques, microchimerism (the proportion of minor variant population is below 1%) has recently gained increasing attention in the field of transplantation. Availability of polymorphic markers, such as deletion insertion or single nucleotide polymorphisms along with a [...] Read more.
Primarily due to recent advances of detection techniques, microchimerism (the proportion of minor variant population is below 1%) has recently gained increasing attention in the field of transplantation. Availability of polymorphic markers, such as deletion insertion or single nucleotide polymorphisms along with a vast array of high sensitivity detection techniques, allow the accurate detection of small quantities of donor- or recipient-related materials. This diagnostic information can improve monitoring of allograft injuries in solid organ transplantations (SOT) as well as facilitate early detection of relapse in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present review, genetic marker and detection platform options applicable for microchimerism detection are discussed. Furthermore, current results of relevant clinical studies in the context of microchimerism and SOT or allo-HSCT respectively are also summarized. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
Open AccessReview
Liquid Biopsy as a Tool for Differentiation of Leiomyomas and Sarcomas of Corpus Uteri
Int. J. Mol. Sci. 2019, 20(15), 3825; https://doi.org/10.3390/ijms20153825 - 05 Aug 2019
Cited by 4
Abstract
Utilization of liquid biopsy in the management of cancerous diseases is becoming more attractive. This method can overcome typical limitations of tissue biopsies, especially invasiveness, no repeatability, and the inability to monitor responses to medication during treatment as well as condition during follow-up. [...] Read more.
Utilization of liquid biopsy in the management of cancerous diseases is becoming more attractive. This method can overcome typical limitations of tissue biopsies, especially invasiveness, no repeatability, and the inability to monitor responses to medication during treatment as well as condition during follow-up. Liquid biopsy also provides greater possibility of early prediction of cancer presence. Corpus uteri mesenchymal tumors are comprised of benign variants, which are mostly leiomyomas, but also a heterogenous group of malignant sarcomas. Pre-surgical differentiation between these tumors is very difficult and the final description of tumor characteristics usually requires excision and histological examination. The leiomyomas and malignant leiomyosarcomas are especially difficult to distinguish and can, therefore, be easily misdiagnosed. Because of the very aggressive character of sarcomas, liquid biopsy based on early diagnosis and differentiation of these tumors would be extremely helpful. Moreover, after excision of the tumor, liquid biopsy can contribute to an increased knowledge of sarcoma behavior at the molecular level, especially on the formation of metastases which is still not well understood. In this review, we summarize the most important knowledge of mesenchymal uterine tumors, the possibilities and benefits of liquid biopsy utilization, the types of molecules and cells that can be analyzed with this approach, and the possibility of their isolation and capture. Finally, we review the typical abnormalities of leiomyomas and sarcomas that can be searched and analyzed in liquid biopsy samples with the final aim to pre-surgically differentiate between benign and malignant mesenchymal tumors. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
Open AccessReview
Cell-Free Nucleic Acids and their Emerging Role in the Pathogenesis and Clinical Management of Inflammatory Bowel Disease
Int. J. Mol. Sci. 2019, 20(15), 3662; https://doi.org/10.3390/ijms20153662 - 26 Jul 2019
Cited by 4
Abstract
Cell-free nucleic acids (cfNAs) are defined as any nucleic acids that are present outside the cell. They represent valuable biomarkers in various diagnostic protocols such as prenatal diagnostics, the detection of cancer, and cardiovascular or autoimmune diseases. However, in the current literature, little [...] Read more.
Cell-free nucleic acids (cfNAs) are defined as any nucleic acids that are present outside the cell. They represent valuable biomarkers in various diagnostic protocols such as prenatal diagnostics, the detection of cancer, and cardiovascular or autoimmune diseases. However, in the current literature, little is known about their implication in inflammatory bowel disease (IBD). IBD is a group of multifactorial, autoimmune, and debilitating diseases with increasing incidence worldwide. Despite extensive research, their etiology and exact pathogenesis is still unclear. Since cfNAs were observed in other autoimmune diseases and appear to be relevant in inflammatory processes, their role in the pathogenesis of IBD has also been suggested. This review provides a summary of knowledge from the available literature about cfDNA and cfRNA and the structures involving them such as exosomes and neutrophil extracellular traps and their association with IBD. Current studies showed the promise of cfNAs in the management of IBD not only as biomarkers distinguishing patients from healthy people and differentiating active from inactive disease state, but also as a potential therapeutic target. However, the detailed biological characteristics of cfNAs need to be fully elucidated in future experimental and clinical studies. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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Open AccessReview
Exosomes-Associated DNA—New Marker in Pregnancy Complications?
Int. J. Mol. Sci. 2019, 20(12), 2890; https://doi.org/10.3390/ijms20122890 - 13 Jun 2019
Cited by 11
Abstract
Despite a large number of studies, the etiology of pregnancy complications remains unknown. The involvement of cell-free DNA or fetal cell-free DNA in the pathogenesis of pregnancy complications is currently being hypothesized. Cell-free DNA occurs in different forms—free; part of neutrophil extracellular traps; [...] Read more.
Despite a large number of studies, the etiology of pregnancy complications remains unknown. The involvement of cell-free DNA or fetal cell-free DNA in the pathogenesis of pregnancy complications is currently being hypothesized. Cell-free DNA occurs in different forms—free; part of neutrophil extracellular traps; or as recently discovered, carried by extracellular vesicles. Cell-free DNA is believed to activate an inflammatory pathway, which could possibly cause pregnancy complications. It could be hypothesized that DNA in its free form could be easily degraded by nucleases to prevent the inflammatory activation. However, recently, there has been a growing interest in the role of exosomes, potential protectors of cell-free DNA, in pregnancy complications. Most of the interest from recent years is directed towards the micro RNA carried by exosomes. However, exosome-associated DNA in relation to pregnancy complications has not been truly studied yet. DNA, as an important cargo of exosomes, has been so far studied mostly in cancer research. This review collects all the known information on the topic of not only exosome-associated DNA but also some information on vesicles-associated DNA and the studies regarding the role of exosomes in pregnancy complications from recent years. It also suggests possible analysis of exosome-associated DNA in pregnancy from plasma and emphasizes the importance of such analysis for future investigations of pregnancy complications. A major obstacle to the advancement in this field is the proper uniformed technique for exosomes isolation. Similarly, the sensitivity of methods analyzing a small fraction of DNA, potentially fetal DNA, carried by exosomes is variable. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
Open AccessReview
Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management
Int. J. Mol. Sci. 2019, 20(12), 2878; https://doi.org/10.3390/ijms20122878 - 13 Jun 2019
Cited by 12
Abstract
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, [...] Read more.
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management. Full article
(This article belongs to the Special Issue Cell-Free Nucleic Acids) Printed Edition available
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