Prostate-derived circulating microRNAs add prognostic value to prostate cancer risk calculators

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Prostate cancer is a leading cause of cancer death in American men.
• Accurate risk stratification is crucial for managing prostate cancer, but biopsy alone has limitations.
• Active surveillance is a viable option for low-risk disease, yet its definitive determination is challenging.

Purpose of the Study:

• To identify prostate-derived microRNAs in patient serum and extracellular vesicles.
• To evaluate if these microRNAs enhance existing clinical risk calculators for prostate cancer prognosis.
• To assess the diagnostic potential of circulating microRNAs for differentiating indolent from aggressive prostate cancer.

Main Methods:

• Small RNA sequencing was used to identify microRNAs in prostate cancer explants and cells.
• A custom microRNA PCR panel was developed for abundant microRNAs.
• Circulating microRNAs were quantified in whole serum and serum extracellular vesicles from a diverse cohort of men diagnosed with prostate cancer.

Main Results:

• Levels of specific circulating microRNAs differed significantly between indolent and aggressive prostate cancer.
• The inclusion of these microRNAs improved the area under the curve (AUC) for pretreatment prostate cancer nomograms.
• MicroRNAs within extracellular vesicles demonstrated the highest improvement in AUC (0.739) compared to nomograms alone (0.561).

Conclusions:

• Quantifying microRNAs in serum extracellular vesicles is a clinically feasible assay.
• This method provides valuable additional information for prostate cancer risk stratification.
• Circulating microRNAs show promise as non-invasive biomarkers for improved prostate cancer prognosis.