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  • br There are several limitations to the

    2022-09-15


    There are several limitations to the current study. The sample size is modest due to the requirement that patient must have post-DRE urine supernatant available since we did not have sufficient quantities of urinary cell sediment available for miRNA analysis. Although the 3-marker panel requires additional validation, the main purpose of this study is the exploration of combining urinary epigenetic biomarkers for prediction of reclassification. We have suc-cessfully shown that assessing 2 different epigenetic markers from post-DRE urine are possible and predictive of CaP progression. However, further investigation is required for validation of these findings. Also, there is no consensus on an endogenous control for urinary miRNAs. Therefore, we opted to use a spike-in RNA as previously described to control for technical variability among samples during proc-essing and analysis. This may not account for endogenous MCC950 differences among patients. Lastly, as AS is a continuing process, we do not know if patients with high 3-marker panel score who were not reclassified were truly indolent. However, ongoing follow-up for these patients will address this issue. It is possible that some or all these patients may experience reclassification in the future.
    5. Conclusions
    We have shown that it is possible to detect miRNAs in the urinary supernatant and that combining urinary cell-free miRNA and sediment DNA methylation is a valid approach to identify AS patients at increased risk for reclassification. Once validated, our 3-marker panel, with its high NPV, could be used to identify AS patients who are unlikely to reclassify so that they may be monitored less intensely, 
    decreasing morbidity and costs, but further prospective con-firmation will be required.
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