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22 pages, 1396 KB

Open AccessReview

Cell-Free Nucleic Acids for Early Diagnosis of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

by Xiaodan Zhang, Yuee Cai, Brian Hon Man Sit, Rain Xiaoyu Jian, Yasine Malki, Yilin Zhang, Christopher Chi Yat Ong, Qianyun Li, Rex Pui Kin Lam and Timothy Hudson Rainer

Int. J. Mol. Sci. 2025, 26(4), 1530; https://doi.org/10.3390/ijms26041530 - 12 Feb 2025

Cited by 3 | Viewed by 2259

Abstract

Rapid identification of acute ischemic stroke (AIS) is challenging in both pre-hospital and hospital settings. We aimed to identify the most promising cell-free nucleic acids (cfNAs) as diagnostic biomarkers for IS within 72 h from symptom onset. We searched PubMed, Web of Science, [...] Read more.

Rapid identification of acute ischemic stroke (AIS) is challenging in both pre-hospital and hospital settings. We aimed to identify the most promising cell-free nucleic acids (cfNAs) as diagnostic biomarkers for IS within 72 h from symptom onset. We searched PubMed, Web of Science, EMBASE, and Cochrane Library for published articles that evaluated blood cfNAs in the early diagnosis of AIS until 10 May 2023. The diagnostic performances of individual cfNAs were pooled by random-effects meta-analysis based on the fold change of biomarkers’ level between AIS and non-AIS patients. Of 2955 records, 66 articles reporting 143 different cfNAs met the inclusion criteria. The median sample size was 110, and 21.4% of the studies performed validation. Among selected high-quality studies, miR-106b-5p, miR-124, miR-155, lncRNA H19, and cfDNA showed good diagnostic performance. Data from four studies on cfDNA involving 355 AIS patients and 97 controls were pooled in the meta-analysis, which showed a significant fold change between AIS and controls (pooled ratio 1.48, 95% confidence interval 1.23–1.79, p < 0.001). This review highlights that cfDNA, miR-106b-5p, miR-124, miR-155, and lncRNA H19 are the most promising biomarkers for AIS diagnosis, and further research is needed for verification. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2025)

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12 pages, 753 KB

Open AccessReview

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review

by Niccolò Morisi, Grazia Maria Virzì, Marco Ferrarini, Gaetano Alfano, Monica Zanella, Claudio Ronco and Gabriele Donati

Genes 2024, 15(5), 553; https://doi.org/10.3390/genes15050553 - 26 Apr 2024

Cited by 4 | Viewed by 2511

Abstract

Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal [...] Read more.

Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. Conclusions: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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25 pages, 453 KB

Open AccessReview

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer

by Anelis Maria Marin, Heloisa Bruna Soligo Sanchuki, Guilherme Naccache Namur, Miyuki Uno, Dalila Luciola Zanette and Mateus Nóbrega Aoki

Biomedicines 2023, 11(4), 1069; https://doi.org/10.3390/biomedicines11041069 - 1 Apr 2023

Cited by 6 | Viewed by 3566

Abstract

A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used [...] Read more.

A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used for the early detection, staging, treatment monitoring, and prognosis of PCa. A novel approach called liquid biopsy has emerged in recent years, which is a less- or non-invasive procedure since it focuses on plasmatic biomarkers such as DNA and RNA. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) have been identified such as DNA, mRNA, and non-coding RNA (miRNA and lncRNA). The presence of these molecules encouraged researchers to investigate their potential as biomarkers. In this article, we focused on circulating cfNAs as plasmatic biomarkers of PCa and analyzed their advantages compared to traditional biopsy methods. Full article

(This article belongs to the Special Issue Diagnostic and Therapeutic Approach to Pancreatic Cancer)

8 pages, 1507 KB

Open AccessCommunication

Isolation and Quantification of Plasma Cell-Free DNA Using Different Manual and Automated Methods

by Eleni Polatoglou, Zsuzsanna Mayer, Vida Ungerer, Abel J. Bronkhorst and Stefan Holdenrieder

Diagnostics 2022, 12(10), 2550; https://doi.org/10.3390/diagnostics12102550 - 20 Oct 2022

Cited by 33 | Viewed by 6798

Abstract

Plasma cell-free DNA (cfDNA) originates from various tissues and cell types and can enable minimally invasive diagnosis, treatment and monitoring of cancer and other diseases. Proper extraction of cfDNA is critical to obtain optimal yields and purity. The goal of this study was [...] Read more.

Plasma cell-free DNA (cfDNA) originates from various tissues and cell types and can enable minimally invasive diagnosis, treatment and monitoring of cancer and other diseases. Proper extraction of cfDNA is critical to obtain optimal yields and purity. The goal of this study was to compare the performance of six commercial cfDNA kits to extract pure, high-quality cfDNA from human plasma samples and evaluate the quantity and size profiles of cfDNA extracts—among them, two spin-column based, three magnetic bead-based and two automatic magnetic bead-based methods. Significant differences were observed in the yield of DNA among the different extraction kits (up to 4.3 times), as measured by the Qubit Fluorometer and Bioanalyzer. All kits isolated mostly small fragments corresponding to mono-nucleosomal sizes. The highest yield and reproducibility were obtained by the manual QIAamp Circulating Nucleic Acid Kit and automated MagNA Pure Total NA Isolation Kit. The results highlight the importance of standardizing preanalytical conditions depending on the requirements of the downstream applications. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids—New Insights into Physico-Chemical Properties, Analytical Considerations, and Clinical Applications)

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13 pages, 1068 KB

Open AccessArticle

Analytic and Clinical Validation of a Pan-Cancer NGS Liquid Biopsy Test for the Detection of Copy Number Amplifications, Fusions and Exon Skipping Variants

by Audrey Audetat, Chérie Tschida, Sarah Kreston, Adam Stephen, Brittany D’Alessio, Madeline Bondy, Leisa Jackson, Hestia Mellert, Niki Givens, Ubaradka G. Sathyanarayana and Gary A. Pestano

Diagnostics 2022, 12(3), 729; https://doi.org/10.3390/diagnostics12030729 - 17 Mar 2022

Cited by 2 | Viewed by 4189

Abstract

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes [...] Read more.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1; exon skipping: MET exon 14; CNAs: HER2, CDK6, EGFR, MYC, and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold was three copies) and was verified using three additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with three additional CNAs. In repeatability and intermediate precision (within lab) studies, all fusion/skipping variants were detected in all runs and all days of testing (n = 18/18; 100%); average CV for repeatability was 20.5% (range 8.7–34.8%), and for intermediate precision it was 20.8% (range 15.7–30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, the average CV was 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for intermediate precision. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the serial detection of clinically relevant variants in cancer. Full article

(This article belongs to the Topic Cancer Biology and Therapy)

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43 pages, 2780 KB

Open AccessReview

Technical and Methodological Aspects of Cell-Free Nucleic Acids Analyzes

by Zuzana Pös, Ondrej Pös, Jakub Styk, Angelika Mocova, Lucia Strieskova, Jaroslav Budis, Ludevit Kadasi, Jan Radvanszky and Tomas Szemes

Int. J. Mol. Sci. 2020, 21(22), 8634; https://doi.org/10.3390/ijms21228634 - 16 Nov 2020

Cited by 41 | Viewed by 7966

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development)

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20 pages, 988 KB

Open AccessReview

Circulating Cell-Free Nucleic Acids: Main Characteristics and Clinical Application

by Melinda Szilágyi, Ondrej Pös, Éva Márton, Gergely Buglyó, Beáta Soltész, Judit Keserű, András Penyige, Tomas Szemes and Bálint Nagy

Int. J. Mol. Sci. 2020, 21(18), 6827; https://doi.org/10.3390/ijms21186827 - 17 Sep 2020

Cited by 154 | Viewed by 14273

Abstract

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to [...] Read more.

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field. Full article

(This article belongs to the Special Issue Cell-Free Nucleic Acids in the Molecular Pathogenesis of Diseases Development)

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21 pages, 979 KB

Open AccessReview

Cell-Free Nucleic Acids and their Emerging Role in the Pathogenesis and Clinical Management of Inflammatory Bowel Disease

by Zuzana Kubiritova, Jan Radvanszky and Roman Gardlik

Int. J. Mol. Sci. 2019, 20(15), 3662; https://doi.org/10.3390/ijms20153662 - 26 Jul 2019

Cited by 39 | Viewed by 6322

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)

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