Prostate Cancer Field Effect: Common Gene Expression Alterations in Prostate Cancer and Benign Prostatic Tissue
Farhad Kosari, Christine M Ida, Jeffrey Karnes, Stephen J Murphy, George Vasmatzis, John C Cheville. Mayo Clinic, Rochester, MN
Background: Prostate cancer field effect alterations provide important cludes regarding cancer initiation, and may provide a role in chemoprevention and early detection. Field effect biomarkers are lacking due to small sample sets used for identification of candidate markers and limited independent validation. The objective of this study was to identify common gene alterations between prostate cancer and adjacent benign tissue in a large set of patient samples and to validate these markers with an independent group of patient samples.
Design: Microarray experments were performed using Affymetrix U133Plus2 chips on benign prostate tissues from patients free of cancer (BP; n=28), prostate cancer from radical prostatectomy specimens (PCa; n=32) and benign posterior zone prostatic tissues from radical prostatectomy specimens (BPC; n=33). The candidate biomarkers that exhibited the greatest difference in expression in PCa and BPC relative to BP were validated in an independent set of BPC (n=33) and BP (n=18) using quantitative RT-PCR. Logistic regression modeling was performed separately on both the validation sample set and microarray data set to determine highest AUC for the association of BPC and PCa. Our results were also evaluated using an external public microarray dataset.
Results: Validated biomarkers included four up-regulated genes and three down-regulated non-exonic sequences not previously associated with PCa field effect. The logistic regression model based on CCNB1 and non-exonic sequences of NACA locus discriminated betwen benign prostate tissue from men with and without PCa in the quantiative PCR validation set with an AUC of 0.84, and the external microarray dataset achieved an AUC of 0.90.
Conclusions: This study confirms the presence of prostate cancer field effect, and identifies validated biomarkers in benign prostate tissue associated with the presence of prostate cancer in radical prostatectomy specimens. Further work is needed to determine the significance of these changes in prostate needle biopsy specimens.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 178, Wednesday Afternoon