Dataset Information

The Translational Potential of Electrochemical DNA-Based Liquid Biopsy.

ABSTRACT: Latest technological advancement has tremendously expanded the knowledge on the composition of body fluids and the cancer-associated changes, which has fueled the replacement of invasive biopsies with liquid biopsies by using appropriate specific receptors. DNA emerges as a versatile analytical reagent in electrochemical devices for hybridization-based or aptamer-based recognition of all kind of biomarkers. In this mini review, we briefly introduce the current affordable targets (tumor-derived nucleic acids, circulating tumor cells and exosomes) in body fluids, and then we provide an overview of selected electrochemical methods already applied in clinical samples by dividing them into three large categories according to sample type: red (blood), yellow (urine), and white (saliva and sweat) diagnostics. This review focuses on the hurdles of the complex matrices rather than a comprehensive and detailed revision of the format schemes of DNA-based electrochemical sensing. This diverse perspective compiles some challenges that are often forgotten and critically underlines real sample analysis or clinical validation assays. Finally, the needs and trends to reach the market are briefly outlined.

SUBMITTER: Miranda-Castro R

PROVIDER: S-EPMC7099045 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Translational Potential of Electrochemical DNA-Based Liquid Biopsy.

Miranda-Castro Rebeca R Palchetti Ilaria I de-Los-Santos-Álvarez Noemí N

Frontiers in chemistry 20200320

Latest technological advancement has tremendously expanded the knowledge on the composition of body fluids and the cancer-associated changes, which has fueled the replacement of invasive biopsies with liquid biopsies by using appropriate specific receptors. DNA emerges as a versatile analytical reagent in electrochemical devices for hybridization-based or aptamer-based recognition of all kind of biomarkers. In this mini review, we briefly introduce the current affordable targets (tumor-derived n ...[more]

PMID: 32266206

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Project description:BackgroundUveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations.MethodsWe used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15).ResultsThe in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors.ConclusionsWe report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.

Dataset Information

The Translational Potential of Electrochemical DNA-Based Liquid Biopsy.

Publications

The Translational Potential of Electrochemical DNA-Based Liquid Biopsy.

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