Abstract | BACKGROUND:
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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
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Authors | Darko Stefanovski, George Tang, Kolja Wawrowsky, Raymond C Boston, Nils Lambrecht, Jian Tajbakhsh |
Journal | Oncotarget
(Oncotarget)
Vol. 8
Issue 34
Pg. 57278-57301
(Aug 22 2017)
ISSN: 1949-2553 [Electronic] United States |
PMID | 28915670
(Publication Type: Journal Article)
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