Publikácie

@article{Gazdarica2024,

title = {Insights into non-informative results from non-invasive prenatal screening through gestational age, maternal BMI, and age analyses},

author = {J. Gazdarica and N. Forgacova and T. Sladecek and M. Kucharik and J. Budis and M. Hyblova and M. Sekelska and A. Gnip and G. Minarik and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85187162464&doi=10.1371%2fjournal.pone.0280858&partnerID=40&md5=c7288799cea18fb3514ec062aa42a91f},

doi = {10.1371/journal.pone.0280858},

issn = {19326203},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {PLoS ONE},

volume = {19},

number = {3 March},

publisher = {Public Library of Science},

abstract = {The discovery of cell-free fetal DNA fragments in the maternal plasma initiated a novel testing method in prenatal care, called non-invasive prenatal screening (NIPS). One of the limitations of NIPS is the necessity for a sufficient proportion of fetal fragments in the analyzed circulating DNA mixture (fetal fraction), otherwise, the sample is uninterpretable. We present the effect of gestational age, maternal body mass index (BMI), and maternal age on the fetal fraction (FF) of the sample. We retrospectively analyzed data from 5543 pregnant women with a single male fetus who underwent NIPS from which 189 samples received a repeat testing due to an insufficient FF. We showed the relationship between the failure rate of the samples after the repeated analysis, the FF, and the gestational age at the first sampling. Next, we found that different maternal BMI categories affect the FF and thus the chance of an informative redraw. A better understanding of the factors affecting the FF will reduce the number of non-informative calls from repeated analyzes. In this study, we provide helpful information to clinicians on how to approach non-informative analyses. © 2024 Gazdarica et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},

keywords = {Aneuploidy, Cell-free nucleic acids, Prenatal diagnosis},

pubstate = {published},

tppubtype = {article}

}

@article{Rendek2024b,

title = {Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics},

author = {T. Rendek and O. Pos and T. Duranova and R. Saade and J. Budis and V. Repiska and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85195678349&doi=10.3390%2fcancers16112001&partnerID=40&md5=a00b727d255d45e6c52a69ea1697e97a},

doi = {10.3390/cancers16112001},

issn = {20726694},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Cancers},

volume = {16},

number = {11},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, and adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence of malignity regardless of its type and location while leveraging blood-based liquid biopsies as a method to obtain analytical samples. However, technical difficulties, costs and challenges resulting from biological variations, tumor heterogeneity, and exogenous factors persist. This method exploits the mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, and high background noise. This review explores cfDNA methylation’s origins, means of detection, and profiling for cancer diagnostics. The critical evaluation of currently available multi-cancer early detection methods (MCEDs) as well as tests targeting single genes, emphasizing their potential and limits to refine strategies for early cancer detection, are explained. The current methodology limitations, workflows, comparisons of clinically approved liquid biopsy-based methylation tests for cancer, their utilization in companion diagnostics as well as the biological limitations of the epigenetics approach are discussed, aiming to help healthcare providers as well as researchers to orient themselves in this increasingly complex and evolving field of diagnostics. © 2024 by the authors.},

keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology, Review},

pubstate = {published},

tppubtype = {article}

}

@article{Soltész2022,

title = {The role of exosomes in cancer progression},

author = {B. Soltész and G. Buglyó and N. Németh and M. Szilágyi and O. Pös and T. Szemes and I. Balogh and B. Nagy},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85121366077&doi=10.3390%2fijms23010008&partnerID=40&md5=a6c0cdd2a0624326aa4378c4af43611b},

doi = {10.3390/ijms23010008},

issn = {16616596},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

number = {1},

publisher = {MDPI},

abstract = {Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non‐invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell‐to‐cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next‐generation treatment of cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Styk2022,

title = {Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer},

author = {J. Styk and G. Buglyó and O. Pös and Á. Csók and B. Soltész and P. Lukasz and V. Repiská and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136586949&doi=10.3390%2fcancers14153712&partnerID=40&md5=c1693e930ca57ea69fb9f5147e1de219},

doi = {10.3390/cancers14153712},

issn = {20726694},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cancers},

volume = {14},

number = {15},

publisher = {MDPI},

abstract = {Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management. © 2022 by the authors.},

keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Maronek2021,

title = {Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice},

author = {M Maronek and B Gromova and R Liptak and B Konecna and M Pastorek and B Cechova and M Harsanyova and J Budis and D Smolak and J Radvanszky and T Szemes and J Harsanyiova and A Kralova Trancikova and R Gardlik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099721641&doi=10.3390%2fcells10010081&partnerID=40&md5=e2a2d57bcd02c36a1091367862022bb1},

doi = {10.3390/cells10010081},

issn = {20734409},

year  = {2021},

date = {2021-01-01},

journal = {Cells},

volume = {10},

number = {1},

publisher = {NLM (Medline)},

abstract = {Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.},

keywords = {Body fluids, Cell-free nucleic acids},

pubstate = {published},

tppubtype = {article}

}

@article{Kucharík2021,

title = {Copy number variant detection with low-coverage whole-genome sequencing represents a viable alternative to the conventional array-cgh},

author = {M Kucharík and J Budiš and M Hýblová and G Minárik and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109087040&doi=10.3390%2fdiagnostics11040708&partnerID=40&md5=6fdfa35027032bf889399d967bb1cce9},

doi = {10.3390/diagnostics11040708},

issn = {20754418},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Diagnostics},

volume = {11},

number = {4},

publisher = {MDPI AG},

abstract = {Copy number variations (CNVs) represent a type of structural variant involving alterations in the number of copies of specific regions of DNA that can either be deleted or duplicated. CNVs contribute substantially to normal population variability, however, abnormal CNVs cause numerous genetic disorders. At present, several methods for CNV detection are applied, ranging from the conventional cytogenetic analysis, through microarray-based methods (aCGH), to next-generation sequencing (NGS). In this paper, we present GenomeScreen, an NGS-based CNV detection method for low-coverage, whole-genome sequencing. We determined the theoretical limits of its accuracy and obtained confirmation in an extensive in silico study and in real patient samples with known genotypes. In theory, at least 6 M uniquely mapped reads are required to detect a CNV with the length of 100 kilobases (kb) or more with high confidence (Z-score > 7). In practice, the in silico analysis required at least 8 M to obtain >99% accuracy (for 100 kb deviations). We compared GenomeScreen with one of the currently used aCGH methods in diagnostic laboratories, which has mean resolution of 200 kb. GenomeScreen and aCGH both detected 59 deviations, while GenomeScreen furthermore detected 134 other (usually) smaller variations. When compared to aCGH, overall performance of the proposed GenemoScreen tool is comparable or superior in terms of accuracy, turn-around time, and cost-effectiveness, thus providing reasonable benefits, particularly in a prenatal diagnosis setting. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Cell-free nucleic acids, Computational method, Copy number variation, Liquid biopsy, Non-invasive prenatal testing},

pubstate = {published},

tppubtype = {article}

}

@article{Pös20201,

title = {Technical and methodological aspects of cell‐free nucleic acids analyzes},

author = {Z Pös and O Pös and J Styk and A Mocova and L Strieskova and J Budis and L Kadasi and J Radvanszky and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85096148893&doi=10.3390%2fijms21228634&partnerID=40&md5=826434c64ac9dbe5f81fc0ee5b62eaa3},

doi = {10.3390/ijms21228634},

issn = {16616596},

year  = {2020},

date = {2020-01-01},

journal = {International Journal of Molecular Sciences},

volume = {21},

number = {22},

pages = {1-43},

publisher = {MDPI AG},

abstract = {Analyzes of cell‐free nucleic acids (cfNAs) have shown huge potential in many biomedical applications, gradually entering several fields of research and everyday clinical care. Many biological properties of cfNAs can be informative to gain deeper insights into the function of the organism, such as their different types (DNA, RNAs) and subtypes (gDNA, mtDNA, bacterial DNA, miRNAs, etc.), forms (naked or vesicle bound NAs), fragmentation profiles, sequence composition, epigenetic modifications, and many others. On the other hand, the workflows of their analyzes comprise many important steps, from sample collection, storage and transportation, through extraction and laboratory analysis, up to bioinformatic analyzes and statistical evaluations, where each of these steps has the potential to affect the outcome and informational value of the performed analyzes. There are, however, no universal or standard protocols on how to exactly proceed when analyzing different cfNAs for different applications, at least according to our best knowledge. We decided therefore to prepare an overview of the available literature and products commercialized for cfNAs processing, in an attempt to summarize the benefits and limitations of the currently available approaches, devices, consumables, and protocols, together with various factors influencing the workflow, its processes, and outcomes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Body fluids, Cell-free nucleic acids, Liquid biopsy, Non-invasive prenatal testing, Review},

pubstate = {published},

tppubtype = {article}

}

@article{Sedlackova20141543,

title = {Selection of an optimal method for co-isolation of circulating DNA and miRNA from the plasma of pregnant women},

author = {T Sedlackova and G Repiska and G Minarik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84908102134&doi=10.1515%2fcclm-2014-0021&partnerID=40&md5=ff635286396a625ebe2934f00e7b7772},

doi = {10.1515/cclm-2014-0021},

issn = {14346621},

year  = {2014},

date = {2014-01-01},

journal = {Clinical Chemistry and Laboratory Medicine},

volume = {52},

number = {11},

pages = {1543-1548},

publisher = {Walter de Gruyter GmbH},

abstract = {Background: Circulating nucleic acids acquired non-invasively have been confirmed as useful biomarkers in cancer and prenatal medicine. The most important molecules in the field of circulating nucleic acids research are circulating DNA and miRNA. In this study, the possibility of co-isolation of total circulating DNA, cell-free fetal DNA and miRNA from the plasma of pregnant women was tested, and the yields of co-isolated circulating nucleic acids using two commercial kits and three protocols were compared. 

Methods: Cell-free fetal DNA and miRNA from the plasma of pregnant women carrying male fetuses were co-isolated with the miRCURY™ RNA Isolation Kit according to the original protocol and the QIAamp Circulating Nucleic Acid Kit (CNA kit) according to the manufacturer's protocol for DNA isolation and miRNA isolation. For comparison of DNA isolation, the AR and DYS14 gene-based assays were used for the detection and quantification of total circulating and cell-free fetal DNA. For miRNA detection and quantification, the miR-16 and miR-451 assays were used. Results: Two different protocols for isolation using the CNA kit did not significantly differ in the yields of isolated tcDNA and cffDNA; however, the amount of isolated cffDNA using the miRCURY™ RNA Isolation Kit was significantly less (p<0.05},

keywords = {Cell-free nucleic acids, Liquid biopsy, Non-invasive prenatal testing},

pubstate = {published},

tppubtype = {article}

}

@article{Vlková20101030,

title = {Circulating free fetal nucleic acids in maternal plasma and preeclampsia},

author = {B Vlková and T Szemes and G Minárik and J Turňa and P Celec},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77951621628&doi=10.1016%2fj.mehy.2010.01.003&partnerID=40&md5=2fc0136f965402efa4d19525338fde3c},

doi = {10.1016/j.mehy.2010.01.003},

issn = {03069877},

year  = {2010},

date = {2010-01-01},

journal = {Medical Hypotheses},

volume = {74},

number = {6},

pages = {1030-1032},

abstract = {Although preeclampsia represents a major threat for many pregnant women, the pathogenesis of this complication is far from being clear. Recent studies suggest that preeclampsia is an autoimmune disorder. Auto-antibodies against angiotensin receptor might explain some of the pathologic findings associated with preeclampsia. However, the origin of the autoimmune reaction is unknown. Here we hypothesize that circulating fetal RNA in maternal plasma might transfect maternal cells. Expression of fetal specific sequences could lead to an immune reaction breaking the immune tolerance against some antigens. Male fetus bearing pregnancies could be at higher risk of preeclampsia due to expression of Y-specific transcripts. This hypothesis is testable by analyzing antibodies and T-lymphocytes of pregnant women with male and female fetuses. © 2010 Elsevier Ltd.},

keywords = {Cell-free nucleic acids, Non-invasive prenatal testing, Preeclampsia},

pubstate = {published},

tppubtype = {article}

}

@article{Vlková2010258,

title = {Does maternal saliva contain fetal DNA usable for prenatal diagnostics?},

author = {B Vlková and T Szemes and G Minárik and J Turňa and P Celec},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-72449174721&doi=10.1016%2fj.mehy.2009.09.022&partnerID=40&md5=e4a8ec14001f99b11fadd011098f2c5d},

doi = {10.1016/j.mehy.2009.09.022},

issn = {03069877},

year  = {2010},

date = {2010-01-01},

journal = {Medical Hypotheses},

volume = {74},

number = {2},

pages = {258-260},

abstract = {Non-invasive molecular analysis of fetal DNA is the diagnostic goal of prenatal medicine. Circulating fetal DNA can be detected in maternal plasma. Recently, it has been detected in the urine of pregnant women. We hypothesize that fetal DNA is present also in maternal saliva and that advances in stabilization and isolation of nucleic acids from saliva enable non-invasive and repeated sampling for prenatal diagnostics. The hypothesis is testable using saliva samples of pregnant women with confirmed male fetuses. Y-specific sequences should be detectable in salivary DNA. Caution must be given to the prevention of contamination. If proved in large studies, the presence of fetal DNA fragments in maternal saliva would enable a wide range of applications in prenatal medicine. © 2009 Elsevier Ltd. All rights reserved.},

keywords = {Body fluids, Cell-free nucleic acids, Non-invasive prenatal testing, Prenatal diagnosis},

pubstate = {published},

tppubtype = {article}

}