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Cancers
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DNA Methylation Markers in Liquid Biopsies
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DNA Methylation Markers in Liquid Biopsies

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 15411

Special Issue Editor

Prof. Dr. Evi S. Lianidou

E-Mail Website
Guest Editor
Department of Chemistry, Analysis of Circulating Tumor Cells Lab., Laboratory of Analytical Chemistry, University of Athens, 15784 Athens, Greece
Interests: liquid biopsy; circulating tumor cells; circulating tumor DNA; molecular diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liquid biopsy is a highly promising and powerful clinical tool for the real-time follow-up of cancer patients that overcomes many of the limitations of tissue biopsies. Liquid biopsy approaches include the enumeration and molecular characterization of circulating tumor cells (CTCs) and analysis of circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs) that are shed from primary tumors and metastatic sites into peripheral blood. The major advantage of liquid biopsy analysis is that it is minimally invasive and can provide real-time information on tumor characteristics in regular time intervals.

Epigenetic alterations have a high potential to provide a valuable source of innovative biomarkers for cancer due to their stability, frequency, and non-invasive accessibility in bodily fluids. Numerous DNA methylation markers are now being tested in liquid biopsies, especially in ctDNA and CTCs, as potential biomarkers, in various types of cancer. DNA methylation in combination with liquid biopsy is very powerful when it comes to providing circulating epigenetic biomarkers of clinical importance. Blood-based epigenetic biomarkers have high potential for the early detection of cancer since DNA methylation in plasma can be detected early during cancer pathogenesis.

This Special Issue of Cancers encompasses new research articles and timely reviews on the latest findings on DNA methylation markers in liquid biopsies for early detection, prognosis, minimal residual disease, risk of relapse, treatment selection, and resistance.

Prof. Dr. Evi S. Lianidou
Guest Editor

Manuscript Submission Information

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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
  • circulating tumor cells
  • CTCs
  • circulating tumor DNA
  • ctDNA
  • DNA methylation
  • epigenetic alterations
  • prognostic biomarkers
  • predictive biomarkers
  • early detection
  • minimal residual disease

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Published Papers (4 papers)

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Research

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15 pages, 1641 KiB  
Article
Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer
by Victoria Tserpeli, Dimitra Stergiopoulou, Dora Londra, Lydia Giannopoulou, Paul Buderath, Ioanna Balgkouranidou, Nikolaos Xenidis, Christina Grech, Eva Obermayr, Robert Zeillinger, Kitty Pavlakis, Theodoros Rampias, Stylianos Kakolyris, Sabine Kasimir-Bauer and Evi S. Lianidou
Cancers 2022, 14(1), 4; https://doi.org/10.3390/cancers14010004 - 21 Dec 2021
Cited by 15 | Viewed by 3639
Abstract
Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment. Methods: In the present study, we examined [...] Read more.
Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment. Methods: In the present study, we examined the methylation status of six gene promoters (BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44) in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC. Results: We report for the first time that the DNA methylation of SLFN11 in plasma cfDNA was significantly correlated with worse PFS (p = 0.045) in advanced stage HGSOC. Conclusions: Our results strongly indicate that SLFN11 epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of SLFN11 promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer. Full article
(This article belongs to the Special Issue DNA Methylation Markers in Liquid Biopsies)
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18 pages, 2491 KiB  
Article
DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment
by Aliki Ntzifa, Dora Londra, Theodoros Rampias, Athanasios Kotsakis, Vassilis Georgoulias and Evi Lianidou
Cancers 2021, 13(23), 5974; https://doi.org/10.3390/cancers13235974 - 27 Nov 2021
Cited by 13 | Viewed by 3200
Abstract
Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In [...] Read more.
Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (RASSF1A, RASSF10, APC, WIF-1, BRMS1, SLFN11, RARβ, SHISA3, and FOXA1) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (n = 80) and in paired CTCs (n = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (n = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (p = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism. Full article
(This article belongs to the Special Issue DNA Methylation Markers in Liquid Biopsies)
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Review

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26 pages, 1928 KiB  
Review
Methylation Markers in Cutaneous Melanoma: Unravelling the Potential Utility of Their Tracking by Liquid Biopsy
by Valentina Aleotti, Cristina Catoni, Cristina Poggiana, Antonio Rosato, Antonella Facchinetti and Maria Chiara Scaini
Cancers 2021, 13(24), 6217; https://doi.org/10.3390/cancers13246217 - 10 Dec 2021
Cited by 14 | Viewed by 4235
Abstract
Malignant melanoma is the most serious, life-threatening form of all dermatologic diseases, with a poor prognosis in the presence of metastases and advanced disease. Despite recent advances in targeted therapy and immunotherapy, there is still a critical need for a better understanding of [...] Read more.
Malignant melanoma is the most serious, life-threatening form of all dermatologic diseases, with a poor prognosis in the presence of metastases and advanced disease. Despite recent advances in targeted therapy and immunotherapy, there is still a critical need for a better understanding of the fundamental mechanisms behind melanoma progression and resistance onset. Recent advances in genome-wide methylation methods have revealed that aberrant changes in the pattern of DNA methylation play an important role in many aspects of cancer progression, including cell proliferation and migration, evasion of cell death, invasion, and metastasization. The purpose of the current review was to gather evidence regarding the usefulness of DNA methylation tracking in liquid biopsy as a potential biomarker in melanoma. We investigated the key genes and signal transduction pathways that have been found to be altered epigenetically in melanoma. We then highlighted the circulating tumor components present in blood, including circulating melanoma cells (CMC), circulating tumor DNA (ctDNA), and tumor-derived extracellular vesicles (EVs), as a valuable source for identifying relevant aberrations in DNA methylation. Finally, we focused on DNA methylation signatures as a marker for tracking response to therapy and resistance, thus facilitating personalized medicine and decision-making in the treatment of melanoma patients. Full article
(This article belongs to the Special Issue DNA Methylation Markers in Liquid Biopsies)
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13 pages, 924 KiB  
Review
Bridging the Gaps between Circulating Tumor Cells and DNA Methylation in Prostate Cancer
by Bianca C. T. Flores, Margareta P. Correia, José G. Rodríguez, Rui Henrique and Carmen Jerónimo
Cancers 2021, 13(16), 4209; https://doi.org/10.3390/cancers13164209 - 21 Aug 2021
Cited by 8 | Viewed by 3057
Abstract
Prostate cancer is the second most common male malignancy, with a highly variable clinical presentation and outcome. Therefore, diagnosis, prognostication, and management remain a challenge, as available clinical, imaging, and pathological parameters provide limited risk assessment. Thus, many biomarkers are under study to [...] Read more.
Prostate cancer is the second most common male malignancy, with a highly variable clinical presentation and outcome. Therefore, diagnosis, prognostication, and management remain a challenge, as available clinical, imaging, and pathological parameters provide limited risk assessment. Thus, many biomarkers are under study to fill this critical gap, some of them based on epigenetic aberrations that might be detected in liquid biopsies. Herein, we provide a critical review of published data on the usefulness of DNA methylation and circulating tumor cells in diagnosis and treatment decisions in cases of prostate cancer, underlining key aspects and discussing the importance of these advances to the improvement of the management of prostate cancer patients. Using minimally invasive blood tests, the detection of highly specific biomarkers might be crucial for making therapeutic decisions, determining response to specific treatments, and allowing early diagnosis. Full article
(This article belongs to the Special Issue DNA Methylation Markers in Liquid Biopsies)
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