Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue
Technical Report,30 Sep 2011,29 Oct 2016
MAYO CLINIC ROCHESTER MN ROCHESTER United States
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The goal of this project was to develop molecular models to distinguish significant Gleason score 7 and higher prostate cancer PCa from indolent Gleason score 6 PCa using biomarkers in the benign non-neoplastic prostate tissue and in high grade PIN HGPIN samples. Aim1 focused in gene expression and methylation analyses by sequencing in a large set of samples to identify gene expression and epigenetic candidate biomarkers. Most promising gene expression biomarkers which were validated in multiple independent sets were selected to develop two logistic regression models. The model for testing in the bulk tissue incorporated 6 genes, including NAV1, LYST, ADD3, SMC5, CEP350, and KIAA2026. This model was validated in 4 of the 5 datasets we tested. Another model to distinguish HGPIN samples in indolent and significant cases was based on three genes including LRRC4C, SUGT1, and KLHL28 and was validated in an independent dataset. This career development grant was an excellent opportunity for us to study prostate cancer field and to realize the clinical potential of cancer field effect. We were able to obtain a sizable set of data which will be used in future research in projects aimed at prevention of PCa and also early detection of significant PCa.