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Cancers
Special Issues
Liquid Biopsy: Current Status and New Challenges
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Liquid Biopsy: Current Status and New Challenges

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 11574

Special Issue Editors

Dr. María Jose Serrano

E-Mail Website
Guest Editor
Medical and Radiotherapeutic Unit, University Hospital Virgen de las Nieves/GENyO Centre, Avenida de la Ilustración, 114-18016 Granada, Spain
Interests: liquid biopsy; circulating tumor cells (CTCs); platelets educated tumor (PETs); extracellular vesicles (EVs); circulating tumor nucleic acids (ctNA); cancer interception (CI)
Special Issues, Collections and Topics in MDPI journals
Dr. Carmen Garrido Navas

E-Mail Website
Co-Guest Editor
GENyO Centre, Granada, Spain
Interests: liquid biopsy; hepatocarcinoma; colon cancer; molecular biology of cancer; molecular human genetic
Dr. Valeria C. Denninghoff

E-Mail Website
Co-Guest Editor
Fundación Pública Progreso y Salud (FPS). Department of General Surgery, Hospital University Virgen del Rocío/CSIC/ University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
Interests: liquid biopsy; ctDNA; pancreas; molecular human genetic

Special Issue Information

Dear Colleagues,

It is my pleasure to invite you to participate in the development of this Special Issue, which addresses the principal advances and challenges currently facing a liquid biopsy.

Liquid biopsy (LB) has been identified as a critical strategic main in precision medicine (PM). Its use allows us to monitor the patient's evolution in real-time. The most crucial role of the LBs is their use as prognostic and predictive markers in different types of tumors, which makes it possible to know how the disease can evolve and identify the best treatment according to the presence and characteristics of these LBs markers. LBs have been accepted as prognostic and predictive markers in numerous solid tumors, especially in metastatic cancer. Therefore, their use in clinical routine has promoted the need to improve the methodologies for analyzing these markers. Although LBs have as a principal attraction minimal invasiveness and time resolution, most LBs show a common characteristic, "minimal biological amounts" to work, whether we are talking about CTCs, ctDNA, or tumor educated platelets, which make their use difficult. New methodologies applied to analyze LBs have emerged to solve these limitations, including the latest methods of massive sequencing (NGS) or digital PCR. Both allow us to obtain accurate results using minimal samples. The technology accompanies the advance in the clinical implementation of LBs. More importantly, these advances promote the use of the LBs in other fields beyond metastatic cancer and cancer. The detection of minimal residual disease to predict the risk of relapse in solid tumors is one of the main challenges of using LB. It is also interesting that LBs are now open to their use as diagnostic markers in those non-tumoral diseases associated with cancer risk (e.g., colon polyps or lung emphysema) and in cancer interception (the obtention of biological information through a non-invasive biopsy to know the real risk to develop cancer in the individuals).

This Special Issue wants to address the main advances and challenges that the use of liquid biopsy face.

Dr. María Jose Serrano
Dr. Carmen Garrido Navas
Dr. Valeria C. Denninghoff
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liquid biopsy
  • cancer interception
  • molecular analyses
  • minimal residual disease
  • epigenomic
  • transcriptomic

Published Papers (5 papers)

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Research

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12 pages, 2046 KiB  
Article
Impact of cfDNA Reference Materials on Clinical Performance of Liquid Biopsy NGS Assays
by Ariane Hallermayr, Thomas Keßler, Moritz Fujera, Ben Liesfeld, Samuel Bernstein, Simon von Ameln, Denny Schanze, Verena Steinke-Lange, Julia M. A. Pickl, Teresa M. Neuhann and Elke Holinski-Feder
Cancers 2023, 15(20), 5024; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15205024 - 17 Oct 2023
Cited by 1 | Viewed by 1394
Abstract
Background: Liquid biopsy enables the non-invasive analysis of genetic tumor variants in circulating free DNA (cfDNA) in plasma. Accurate analytical validation of liquid biopsy NGS assays is required to detect variants with low variant allele frequencies (VAFs). Methods: Six types of commercial cfDNA [...] Read more.
Background: Liquid biopsy enables the non-invasive analysis of genetic tumor variants in circulating free DNA (cfDNA) in plasma. Accurate analytical validation of liquid biopsy NGS assays is required to detect variants with low variant allele frequencies (VAFs). Methods: Six types of commercial cfDNA reference materials and 42 patient samples were analyzed using a duplex-sequencing-based liquid biopsy NGS assay. Results: We comprehensively evaluated the similarity of commercial cfDNA reference materials to native cfDNA. We observed significant differences between the reference materials in terms of wet-lab and sequencing quality as well as background noise. No reference material resembled native cfDNA in all performance metrics investigated. Based on our results, we established guidelines for the selection of appropriate reference materials for the different steps in performance evaluation. The use of inappropriate materials and cutoffs could eventually lead to a lower sensitivity for variant detection. Conclusion: Careful consideration of commercial reference materials is required for performance evaluation of liquid biopsy NGS assays. While the similarity to native cfDNA aids in the development of experimental protocols, reference materials with well-defined variants are preferable for determining sensitivity and precision, which are essential for accurate clinical interpretation. Full article
(This article belongs to the Special Issue Liquid Biopsy: Current Status and New Challenges)
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13 pages, 1563 KiB  
Article
Uterine Cavity Lavage Mutation Analysis in Lithuanian Ovarian Cancer Patients
by Diana Žilovič, Ieva Vaicekauskaitė, Rūta Čiurlienė, Rasa Sabaliauskaitė and Sonata Jarmalaitė
Cancers 2023, 15(3), 868; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030868 - 30 Jan 2023
Cited by 1 | Viewed by 1325
Abstract
Background: Type II ovarian cancer (OC) is generally diagnosed at an advanced stage, translating into a poor survival rate. Current screening methods for OC have failed to demonstrate a reduction in mortality. The uterine lavage technique has been used to detect tumor-specific TP53 [...] Read more.
Background: Type II ovarian cancer (OC) is generally diagnosed at an advanced stage, translating into a poor survival rate. Current screening methods for OC have failed to demonstrate a reduction in mortality. The uterine lavage technique has been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer (HGSOC). We aimed to pilot whether the detection of TP53 mutation in uterine cavity lavage can be used as a diagnostic method for HGSOC using an expanded gene panel. Methods: In this study 90, uterine lavage and 46 paired biopsy samples were analyzed using next-generation sequencing (NGS) targeting TP53 as well as five additional OC-related genes: BRCA1, BRCA2, PI3KCA, PTEN, and KRAS. Results: Uterine lavage was successfully applied to all patients, and 56 mutations were detected overall. TP53 mutations were detected in 27% (10/37) of cases of type HGSOC; BRCA1 and BRCA2 mutations were also frequent in this group (46%; 17/37). Overall concordance between tissue and liquid biopsy samples was 65.2%. Conclusion: Uterine lavage TP53 mutations in combination with other biomarkers could be a useful tool for the detection of lowly invasive HGSOC. Full article
(This article belongs to the Special Issue Liquid Biopsy: Current Status and New Challenges)
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14 pages, 2760 KiB  
Article
Exosomal and Soluble Programed Death-Ligand 1 (PD-L1) Predicts Responses to Pembrolizumab in Patients with Extranodal NK/T-Cell Lymphoma
by Seok Jin Kim, Kyung Ju Ryu, Bon Park, Sang Eun Yoon, Junhun Cho, Yoon Park and Won Seog Kim
Cancers 2022, 14(22), 5618; https://doi.org/10.3390/cancers14225618 - 16 Nov 2022
Cited by 2 | Viewed by 1468
Abstract
Soluble and exosomal programed death-ligand 1 (PD-L1) can be upregulated in extranodal natural killer/T-cell lymphoma (ENKTL). However, its clinical role in predicting outcomes after pembrolizumab treatment has yet to be studied in ENKTL patients. We investigated the association between pre-treatment soluble and exosomal [...] Read more.
Soluble and exosomal programed death-ligand 1 (PD-L1) can be upregulated in extranodal natural killer/T-cell lymphoma (ENKTL). However, its clinical role in predicting outcomes after pembrolizumab treatment has yet to be studied in ENKTL patients. We investigated the association between pre-treatment soluble and exosomal PD-L1 and outcomes in ENKTL patients who received pembrolizumab as a salvage treatment. The production of soluble and exosomal PD-L1 was analyzed in vitro using an etoposide-resistant ENKTL cell line. Serum levels of soluble and exosomal PD-L1 were measured in patients with relapsed or refractory ENKTL prior to treatment with pembrolizumab. Relapsed or refractory ENKTL patients who received pembrolizumab as a salvage therapy between May 2017 and March 2021 were analyzed at our institute. Soluble and exosomal PD-L1 was significantly higher in serum samples of relapsed or refractory ENKTL patients compared with healthy controls, which is consistent with increased production of soluble and exosomal PD-L1 in an etoposide-resistant ENKTL cell line (SNK6R), which was found to show increased expression of soluble and exosomal PD-L1. Serum-soluble PD-L1 levels were significantly correlated with exosomal PD-L1, and were significantly lower in responders to pembrolizumab compared with non-responders. Longitudinal analysis after pembrolizumab also revealed a relationship between PD-L1 levels and responses. Treatment outcomes and overall survival after pembrolizumab were significantly better in patients with low soluble and exosomal PD-L1. In conclusion, soluble and exosomal PD-L1 can predict responses to pembrolizumab in ENKTL patients, making it a useful pre-treatment biomarker for ENKTL patients receiving pembrolizumab. Full article
(This article belongs to the Special Issue Liquid Biopsy: Current Status and New Challenges)
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12 pages, 24396 KiB  
Article
A Novel, Quick, and Reliable Smartphone-Based Method for Serum PSA Quantification: Original Design of a Portable Microfluidic Immunosensor-Based System
by Francisco Gabriel Ortega, Germán E. Gómez, Coral González-Martinez, Teresa Valero, José Expósito-Hernández, Ignacio Puche, Alba Rodriguez-Martinez, María José Serrano, José Antonio Lorente and Martín A. Fernández-Baldo
Cancers 2022, 14(18), 4483; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184483 - 16 Sep 2022
Cited by 5 | Viewed by 2109
Abstract
We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. [...] Read more.
We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at −100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL−1 to 1500 pg mL−1. The sensitivity was demonstrated by a detection limit of 2 pg mL−1 and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels. Full article
(This article belongs to the Special Issue Liquid Biopsy: Current Status and New Challenges)
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Review

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46 pages, 3601 KiB  
Review
Circulating Exosome Cargoes Contain Functionally Diverse Cancer Biomarkers: From Biogenesis and Function to Purification and Potential Translational Utility
by Megan I. Mitchell, Junfeng Ma, Claire L. Carter and Olivier Loudig
Cancers 2022, 14(14), 3350; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143350 - 10 Jul 2022
Cited by 11 | Viewed by 4009
Abstract
Although diagnostic and therapeutic treatments of cancer have tremendously improved over the past two decades, the indolent nature of its symptoms has made early detection challenging. Thus, inter-disciplinary (genomic, transcriptomic, proteomic, and lipidomic) research efforts have been focused on the non-invasive identification of [...] Read more.
Although diagnostic and therapeutic treatments of cancer have tremendously improved over the past two decades, the indolent nature of its symptoms has made early detection challenging. Thus, inter-disciplinary (genomic, transcriptomic, proteomic, and lipidomic) research efforts have been focused on the non-invasive identification of unique “silver bullet” cancer biomarkers for the design of ultra-sensitive molecular diagnostic assays. Circulating tumor biomarkers, such as CTCs and ctDNAs, which are released by tumors in the circulation, have already demonstrated their clinical utility for the non-invasive detection of certain solid tumors. Considering that exosomes are actively produced by all cells, including tumor cells, and can be found in the circulation, they have been extensively assessed for their potential as a source of circulating cell-specific biomarkers. Exosomes are particularly appealing because they represent a stable and encapsulated reservoir of active biological compounds that may be useful for the non-invasive detection of cancer. T biogenesis of these extracellular vesicles is profoundly altered during carcinogenesis, but because they harbor unique or uniquely combined surface proteins, cancer biomarker studies have been focused on their purification from biofluids, for the analysis of their RNA, DNA, protein, and lipid cargoes. In this review, we evaluate the biogenesis of normal and cancer exosomes, provide extensive information on the state of the art, the current purification methods, and the technologies employed for genomic, transcriptomic, proteomic, and lipidomic evaluation of their cargoes. Our thorough examination of the literature highlights the current limitations and promising future of exosomes as a liquid biopsy for the identification of circulating tumor biomarkers. Full article
(This article belongs to the Special Issue Liquid Biopsy: Current Status and New Challenges)
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