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Prostate cancer diagnosis using epigenetic biomarkers, 3D high-content imaging and probabilistic cell-by-cell classifiers.

ABSTRACT: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue.We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis. We used consecutive biopsies/radical prostatectomies from five patients for building a database of ?140,000 analyzed cells across all tissue compartments and for model development; and from five patients and the two well-characterized HPrEpiC primary and LNCaP cancer cell types for model validation.Principal component analysis presented highest covariability for the four biomarkers 4',6-diamidino-2-phenylindole, 5-methylcytosine, 5-hydroxymethylcytosine, and alpha-methylacyl-CoA racemase in the epithelial tissue compartment. The panel also showed best performance in discriminating between normal and cancer-like cells in prostate tissues with a sensitivity and specificity of 85%, correctly classified 87% of HPrEpiC as healthy and 99% of LNCaP cells as cancer-like, identified a majority of aberrant cells within histopathologically benign tissues at baseline diagnosis of patients that were later diagnosed with adenocarcinoma. Using k-nearest neighbor classifier with cells from an initial patient biopsy, the biomarkers were able to predict cancer stage and grade of prostatic tissue that occurred at later prostatectomy with 79% accuracy.Our approach showed favorable diagnostic values to identify the portion and pathological category of aberrant cells in a small subset of sampled tissue cells, correlating with the degree of malignancy beyond baseline.

SUBMITTER: Stefanovski D

PROVIDER: S-EPMC5593641 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prostate cancer diagnosis using epigenetic biomarkers, 3D high-content imaging and probabilistic cell-by-cell classifiers.

Stefanovski Darko D Tang George G Wawrowsky Kolja K Boston Raymond C RC Lambrecht Nils N Tajbakhsh Jian J

Oncotarget 20170705 34

<h4>Background</h4>Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue.<h4>Method</h4>We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, ...[more]

PMID: 28915670

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Project description:ContextIn addition to genetic alterations, epigenetic alterations play a crucial role during prostate cancer progression. A better understanding of the epigenetic factors that promote prostate cancer progression may lead to the design of rational therapeutic strategies to target prostate cancer more effectively.ObjectiveTo systematically review recent literature on the role of epigenetic factors in prostate cancer and highlight key preclinical and translational data with epigenetic therapies.Evidence acquisitionWe performed a systemic literature search in PubMed. At the request of the editors, we limited our search to articles published between January 2015 and August 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Clinical trials targeting epigenetic factors were retrieved from clinicaltrials.gov.Evidence synthesisWe retrieved 1451 articles, and 62 were finally selected for review. Twelve additional foundational studies outside this time frame were also included. Findings from both preclinical and clinical studies were reviewed and summarized. We also discuss 12 ongoing clinical studies with epigenetic targeted therapies.ConclusionsEpigenetic mechanisms impact prostate cancer progression. Understanding the role of specific epigenetic factors is critical to determine how we may improve prostate cancer treatment and modulate resistance to standard therapies. Recent preclinical studies and ongoing or completed clinical studies with epigenetic therapies provide a useful roadmap for how to best deploy epigenetic therapies clinically to target prostate cancer.Patient summaryEpigenetics is a process by which gene expression is regulated without changes in the DNA sequence itself. Oftentimes, epigenetic changes influence cellular behavior and contribute to cancer development or progression. Understanding how epigenetic changes occur in prostate cancer is the first step toward therapeutic targeting in patients. Importantly, laboratory-based studies and recently completed and ongoing clinical trials suggest that drugs targeting epigenetic factors are promising. More work is necessary to determine whether this class of drugs will add to our existing treatment arsenal in prostate cancer.

Dataset Information

Prostate cancer diagnosis using epigenetic biomarkers, 3D high-content imaging and probabilistic cell-by-cell classifiers.

Publications

Prostate cancer diagnosis using epigenetic biomarkers, 3D high-content imaging and probabilistic cell-by-cell classifiers.

Similar Datasets

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