The Prostate Tumor Microenvironment Exhibits differentially expressed Genes Useful for Diagnosis

EDRN 2010-8011
Mercola, DanUniversity of California Irvine
Multi-gene profile
No design specified.
Prostate and Urologic Cancers Research Group

This protocol for the use of human subjects in a prospective observational clinical trial of a new diagnostic test for prostate cancer that is based on collection and analyzes tumor stroma or microenvironment tissue. No treatment and no devices other than standard of care are proposed. Consenting patients of the UCIMC and the Orange County Urology Associates (OCUA) will be asked to provide an extra or 13th core of tissue during their clinical 12-core biopsy procedure that will be used for research purposes and patient diagnoses, as necessary. All collected tissue will be analyzed in the UCI Pathology Molecular Genetics CLIA lab. The data will be used to determine the probability that the biopsy contains tumor using the SPECS algorithm for determination of “presence of tumor”. In order to validate the accuracy of this diagnosis, the frequency of positive and negative diagnoses will be compared to the true frequency of diagnosis as defined by clinical pathology diagnoses observed in repeat biopsy results of the same cases, i.e. by Chi-square test. All patients will be followed by shadow chart development by entry into the IRB-approved HS# 2005-4806, Dr. Mercola UCI SPECS prostate program database, which is hosted on two servers one maintained by the HSIS group and the other, in compliance with disaster preparedness, is maintained at the Vaccine Research Institute in San Diego, CA 92121 by a co-PI of this study, M. McClelland who is also a UCI Pathology Visiting Professor with an experimental program in Pathology. As will be summarized under risk assessment, the protocol actually reduces the risk of adverse events affecting participating patients by providing clinical data on the 13th biopsy thereby minimizing the risk of a false negative biopsy, now rated at ~30%.

Aim 1. To quantitatively validate the accuracy, sensitivity, and specificity of a 23 gene stroma-based diagnostic profile based on independent test sets of normal prostate tissue and confirmed prostate carcinoma using a blinded sample testing procedures (PRoBE methods). The validation will be extended to independent tumor-adjacent stroma samples of known prognostic value thereby testing the prognostic potential as well as the diagnostic accuracy. Aim 2. Quantitatively validate the 23 gene profile as cell-type-specific using manual microdissection. Aim 3. Prospective Clinical trial in CLIA setting to test the Diagnostic Classifier for diagnostic, early detection, and prognostic accuracy using consented fresh human prostate biopsies of patients slated for repeat biopsy in 6-12 months at UCI and samples provided by Dr. Paul Bower of the Orange County Urology Associates. Aim 4. Test of the hypothesis that TGF-β directs expression of biomarkers that are predictive of outcome.
Expression analysis

No datasets are currently associated with this protocol.

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