A standardized serum bank for obtaining microRNA signatures for assessing prostate cancer risk.
scott perrapato, DO FACOS, Nicholas Farina, PhD, Adrian Berg, MD, Marcia Wills, MD, Jane Lian, PhD.
University of Vermont, burlington, VT, USA.
Background: MicroRNA (miRNA) signatures have been shown to predict long-term risk of breast and other cancers. We hypothesize a subset of cancer-free men at elevated risk ("risk") for developing prostate cancer (First degree relatives) will have a miRNA signature which distinguish them from average risk ("no risk") individuals. Methods and Materials: 1) Serum miRNA development serum microRNA collection, processing, storage (tissue bank) and analysis by recent technologies that are reproducible; 2) Identify microRNA profiles in men at elevated risk for prostate cancer that are distinct from controls; 3) Determine the effect of time from collection, ejaculation and symptomatic benign prostatic hyperplasia on a miRNA signature; 4) Compare in-house qPCR analysis with FirePlex™ Technology to validate miRNA signature components; 5) Determine the relationships between clinical elevated risk categories that are associated with signature miRNAs. Results: This pilot study enrolled a total of 68 cancer-free men, 51 with average risk of prostate cancer and 17 having elevated risk with a family history (First degree relative). The predictive ability of family history was compared to patient age, time from ejaculation, and PSA levels using ROC curves (AUC = 0.55, 0.42, 0.63 respectively). From a literature review, we identified 65 miRNAs associated with prostate cancer development, transition from indolent to aggressive disease, and metastasis. We found miR-141-3p and miR-376c-3p to be elevated ≥ 1.5-fold in the 17 men with a family history as compared to the 51 men with average risk factors. Further, seven miRNAs were expressed at significantly higher levels in a cohort of 15 prostate cancer patients. Four of these miRNAs are detected at lower levels in cancer-free men, independent of risk status. However, three of these miRNAs (let-7c-3p, miR-130a-5p, miR-221-3p) are not significantly different between men with elevated risk and prostate cancer patients, suggesting a function of these in prostate cancer development and future application as clinical biomarkers. Conclusions: a) Successful establishment of scalable serum miRNA analysis that allows expression screening between patient populations with different clinical characteristics to discover miRNA signatures. b) Cancer-free men with a family history of prostate cancer have higher levels of miR-141-3p as compared to average risk. Further, miR-141-3p is well established to elevated in the serum of prostate cancer patients and suggests utility as a clinical biomarker to monitor for predicting future cancer development. c) Demonstration of no effect of ejaculation or symptomatic benign prostatic hyperplasia as an indicator of elevated risk from family history.
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