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Circulating Biomarkers
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Circulating Biomarkers

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 24219

Special Issue Editor

Assoc. Prof. Therese Becker

E-Mail Website
Guest Editor
1. Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
2. School of Medicine, University of Western Sydney, Liverpool, NSW, Australia
3. South Western Medical School, University of New South Wales, Liverpool, Australia
4. CONCERT-Translational Cancer Research Centre, NSW, Australia
Interests: biomarker; liquid biopsy; circulating tumour cells (CTCs); circulating tumor nucleic acids (ctDNA); ddPCR; melanoma; prostate cancer; lung cancer; brain cancer; personalized medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers are biological indicators, and in medicine, they potentially are able to dictate the best patient management and allow for personalised therapy. In recent years, we have been experiencing a revolution of technologies to detect and analyse various biomarkers down to their biochemical and biophysical level. A lot of emphasis is on circulating biomarkers because they can be examined from relatively simple, non-invasive liquid biopsies. Circulating biomarkers carry enormous potential, especially for diseases like cancer, where the cancer itself, in part due to the selective pressure of medication, evolves and changes over time. Liquid biopsies can be taken repeatedly for diagnostic and prognostic purposes and to monitor response to therapy or developing resistance.

In this Special Circulating Biomarkers Issue, we will explore how technologies are refined to investigate established and novel biomarkers from liquid biopsies. We aim to determine and review how well these techniques are implemented in the clinics, with future perspectives on how the research field and clinical applications may develop. Last but not least, we will look at how circulating biomarkers can translate into patient management and disease outcomes and how well they compare on a health economic level with current alternatives.

The science considered here is inclusive and does not aim to restrict authors but rather to open up the Special Issue to as wide an audience as possible. Technical articles progressing recent advances in methodologies are welcome, while biological and medical studies that translate understanding of circulating biomarkers into clinical settings are equally encouraged.

Assoc. Prof.Therese Becker
Guest Editor

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Keywords

  • Liquid biopsy
  • Circulating tumour cell (CTC)
  • Single cell analysis
  • Circulating tumour nucleic acid (ctNA, including ctDNA, ctRNA, ct-mirRNA)
  • Exosomes
  • Extracellular vesicles
  • Plasma/serum cancer antigens
  • Circulating protein markers
  • Blood-based biomarker
  • Circulating lipid markers

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Published Papers (7 papers)

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Research

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12 pages, 863 KiB  
Article
Evaluation of Serum Serotonin as a Biomarker for Myocardial Infarction and Ischemia/Reperfusion Injury
by Marina Rieder, Rosmarie Laumann, Thilo Witsch, Nancy Schanze, Lukas Heger, Christoph B. Olivier, Constantin von zur Muehlen, Christoph Bode, Ingo Ahrens, Achim Lother, Daniel Duerschmied and Marcus Hortmann
Appl. Sci. 2020, 10(18), 6379; https://doi.org/10.3390/app10186379 - 13 Sep 2020
Cited by 3 | Viewed by 2976
Abstract
Background: Activated platelets release serotonin during acute myocardial infarction (AMI), aggravating myocardial damage and ischemia/reperfusion (I/R) injury. However, serum serotonin and its potential role as a biomarker for myocardial infarction and I/R injury have not been studied so far. Methods: In this investigator-initiated [...] Read more.
Background: Activated platelets release serotonin during acute myocardial infarction (AMI), aggravating myocardial damage and ischemia/reperfusion (I/R) injury. However, serum serotonin and its potential role as a biomarker for myocardial infarction and I/R injury have not been studied so far. Methods: In this investigator-initiated pilot study, we examined 38 patients with ST-segment myocardial infarction (STEMI). We determined serum serotonin levels prior to percutaneous coronary intervention and 8, 16, and 24 h afterwards. We studied whether serum serotonin was associated with I/R injury assessed by ECG analysis and by analysis of TIMI myocardial perfusion grade (TMP) and myocardial blush grade (MGB). Serum serotonin levels were compared to an age-matched control group consisting of patients admitted to the emergency department for any other reason than STEMI. Results: Serum serotonin levels were not elevated in the myocardial infarction group compared to the control cohort and they did not show any timeline kinetics after STEMI. They were not associated with the severity of coronary artery disease, the outcome of coronary angiography, the extent of I/R injury, or the degree of heart failure. Conclusions: Serum serotonin is not suitable as a biomarker after myocardial infarction and in the assessment of I/R injury. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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11 pages, 682 KiB  
Article
A Multiplex PCR-Based Next Generation Sequencing-Panel to Identify Mutations for Targeted Therapy in Breast Cancer Circulating Tumor Cells
by André Franken, Mahdi Rivandi, Liwen Yang, Bernadette Jäger, Natalia Krawczyk, Ellen Honisch, Dieter Niederacher, Tanja Fehm and Hans Neubauer
Appl. Sci. 2020, 10(10), 3364; https://doi.org/10.3390/app10103364 - 13 May 2020
Cited by 5 | Viewed by 3600
Abstract
Targeted therapy has become the preferred approach to treat most cancers, including metastatic breast cancer. Using liquid biopsies, which can act as a dynamic diagnostic tool, is an appealing concept to identify effective therapies. In order to identify mutations from circulating tumor cells [...] Read more.
Targeted therapy has become the preferred approach to treat most cancers, including metastatic breast cancer. Using liquid biopsies, which can act as a dynamic diagnostic tool, is an appealing concept to identify effective therapies. In order to identify mutations from circulating tumor cells (CTCs) on single cell level, we have developed a multiplex PCR-based next generation sequencing-panel. The CTCs were enriched using the CellSearch system and isolated by micromanipulation followed by whole genome amplification of their DNA. Afterwards, mutation hotspot regions in the PIK3CA, the ESR1, the AKT1, and the ERBB2 genes were amplified and barcoded. Sequencing was performed on a MiSeq system. The assay was validated with cells from various cell lines displaying the expected mutations. Mutations that provide the basis for potential targeted therapies were detected in 10 out of 13 patients in all analyzed genes. In four patients, mutations in more than one gene were observed—either in the same cell or in different cells, suggesting the presence of different tumor cell clones, which might be targeted with combination therapies. This assay is a time and cost effective tool to investigate the most relevant genomic positions indicative for targeted therapies in metastatic breast cancer. It can support therapy decision to improve the treatment of cancer patients. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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11 pages, 2466 KiB  
Article
Isolation of Circulating Tumor Cells from Glioblastoma Patients by Direct Immunomagnetic Targeting
by David Lynch, Branka Powter, Joseph William Po, Adam Cooper, Celine Garrett, Eng-Siew Koh, Mark Sheridan, James van Gelder, Balsam Darwish, Simon Mckechnie, Renata Bazina, Matthias Jaeger, Tara Laurine Roberts, Paul de Souza and Therese Maria Becker
Appl. Sci. 2020, 10(9), 3338; https://doi.org/10.3390/app10093338 - 11 May 2020
Cited by 13 | Viewed by 4474
Abstract
Glioblastoma (GBM) is the most common form of primary brain cancer in adults and tissue biopsies for diagnostic purposes are often inaccessible. The postulated idea that brain cancer cells cannot pass the blood–brain barrier to form circulating tumor cells (CTCs) has recently been [...] Read more.
Glioblastoma (GBM) is the most common form of primary brain cancer in adults and tissue biopsies for diagnostic purposes are often inaccessible. The postulated idea that brain cancer cells cannot pass the blood–brain barrier to form circulating tumor cells (CTCs) has recently been overthrown and CTCs have been detected in the blood of GBM patients albeit in low numbers. Given the potential of CTCs to be analyzed for GBM biomarkers that may guide therapy decisions it is important to define methods to better isolate these cells. Here, we determined markers for immunomagnetic targeting and isolation of GBM-CTCs and confirmed their utility for CTC isolation from GBM patient blood samples. Further, we identified a new marker to distinguish isolated GBM-CTCs from residual lymphocytes. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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17 pages, 1330 KiB  
Article
Hypermethylation of Circulating Free DNA in Cutaneous Melanoma
by Russell J. Diefenbach, Jenny H. Lee, David Chandler, Yinan Wang, Christian Pflueger, Georgina V. Long, Richard A. Scolyer, Matteo S. Carlino, Alexander M. Menzies, Richard F. Kefford and Helen Rizos
Appl. Sci. 2019, 9(23), 5074; https://doi.org/10.3390/app9235074 - 25 Nov 2019
Cited by 6 | Viewed by 3369
Abstract
Changes in DNA methylation are well documented in cancer development and progression and are typically identified through analyses of genomic DNA. The capability of monitoring tumor-specific methylation changes in circulating tumor DNA (ctDNA) has the potential to improve the sensitivity of ctDNA for [...] Read more.
Changes in DNA methylation are well documented in cancer development and progression and are typically identified through analyses of genomic DNA. The capability of monitoring tumor-specific methylation changes in circulating tumor DNA (ctDNA) has the potential to improve the sensitivity of ctDNA for the diagnosis and prognosis of solid tumors. In this study we profiled the methylation of seven gene targets (all known to be hypermethylated in metastatic melanoma) within the plasma of patients with advanced melanoma using amplicon-based next generation sequencing of bisulfite-treated DNA. Hypermethylation of 6/7 gene targets, including paraoxonase 3 (PON3) was significantly elevated in patients with metastatic melanoma (n = 4) compared to healthy control samples (n = 5). In addition, the degree of hypermethylation of PON3 and MEOX2 were significantly correlated with ctDNA copy number in melanoma patients, confirming the utility of methylated ctDNA in the absence of tumor mutation data for genes such as BRAF, RAS or EGFR. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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15 pages, 186603 KiB  
Article
Immune-Related Circulating miR-125b-5p and miR-99a-5p Reveal a High Recurrence Risk Group of Pancreatic Cancer Patients after Tumor Resection
by Eveline E. Vietsch, Ivana Peran, Mustafa Suker, Thierry P. P. van den Bosch, Fleur van der Sijde, Johan M. Kros, Casper H. J. van Eijck and Anton Wellstein
Appl. Sci. 2019, 9(22), 4784; https://doi.org/10.3390/app9224784 - 8 Nov 2019
Cited by 5 | Viewed by 3092
Abstract
Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model [...] Read more.
Clinical follow-up aided by changes in the expression of circulating microRNAs (miRs) may improve prognostication of pancreatic ductal adenocarcinoma (PDAC) patients. Changes in 179 circulating miRs due to cancer progression in the transgenic KrasG12D/+; Trp53R172H/+; P48-Cre (KPC) animal model of PDAC were analyzed for serum miRs that are altered in metastatic disease. In addition, expression levels of 250 miRs were profiled before and after pancreaticoduodenectomy in the serum of two patients with resectable PDAC with different progression free survival (PFS) and analyzed for changes indicative of PDAC recurrence after resection. Three miRs that were upregulated ≥3-fold in progressive PDAC in both mice and patients were selected for validation in 26 additional PDAC patients before and after resection. We found that high serum miR-125b-5p and miR-99a-5p levels after resection are significantly associated with shorter PFS (HR 1.34 and HR 1.73 respectively). In situ hybridization for miR detection in the paired resected human PDAC tissues showed that miR-125b-5p and miR-99a-5p are highly expressed in inflammatory cells in the tumor stroma, located in clusters of CD79A expressing cells of the B-lymphocyte lineage. In conclusion, we found that circulating miR-125b-5p and miR-99a-5p are potential immune-cell related prognostic biomarkers in PDAC patients after surgery. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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Review

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9 pages, 924 KiB  
Review
Required Evidence for Clinical Applications of Liquid Biopsy Using Especially CTCs in Lung Cancer
by Menno Tamminga and Harry J.M. Groen
Appl. Sci. 2020, 10(11), 3704; https://doi.org/10.3390/app10113704 - 27 May 2020
Cited by 1 | Viewed by 1981
Abstract
As therapies have become more and more dependent on tumor as well as patient characteristics, obtaining tumor material has become of great importance. Liquid biopsies hold much potential as shown by a large amount of evidence across several studies. Clinical applications for circulating [...] Read more.
As therapies have become more and more dependent on tumor as well as patient characteristics, obtaining tumor material has become of great importance. Liquid biopsies hold much potential as shown by a large amount of evidence across several studies. Clinical applications for circulating tumor cells (CTCs) are unfortunately still lacking. In part this is due to a lack of studies comparing liquid biopsies to conventional diagnostics and response measurements as well as studies showing that liquid biopsies can be used to switch therapies leading to improved outcomes. However, liquid biopsies using ctDNA for specific markers such as EGFR, ALK, ROS1 or RET have clinical applications because specific drugs are available. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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6 pages, 540 KiB  
Review
Circulating Tumor Cells in Metastatic Breast Cancer: Clinical Applications and Future Possibilities
by Maggie Banys-Paluchowski, Florian Reinhardt and Tanja Fehm
Appl. Sci. 2020, 10(9), 3311; https://doi.org/10.3390/app10093311 - 9 May 2020
Cited by 10 | Viewed by 3798
Abstract
Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast [...] Read more.
Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast cancer, detection of CTCs correlates with clinical outcome in early and metastatic settings. CTC persistence beyond first cycle of palliative chemotherapy indicates poor response to treatment in metastatic situation. Beyond prognostication and therapy monitoring, CTC counts can guide treatment decisions in hormone receptor positive HER2-negative metastatic breast cancer. Furthermore, CTC-based therapy interventions are currently under investigation in clinical trials. In this review, we focus on the current state of knowledge and possible clinical applications of CTC diagnostics in patients with metastatic breast cancer. Full article
(This article belongs to the Special Issue Circulating Biomarkers)
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