Validation of Molecular Markers of Aggressiveness in Prostate Cancer
A Johnson, N Rosener, A Rizzardi, R Isaksson Vogel, G Metzger, S Schmechel. University of Minnesota, Minneapolis, MN; University of Minnesota, Minnesota, MN
Background: Prostate cancer is heterogeneous with respect to clinical outcome. A minority of patients have clinically aggressive disease resulting in biochemical failure (rising serum prostate specific antigen levels following postoperative low nadir), whereas the majority of patients have non-aggressive disease. Validated molecular markers that may predict aggressive clinical course following prostatectomy are needed.
Design: We have used publicly availabe RNA expression microarray datasets and a method of Ordered Gene List (OGL) analysis to identify genes whose expression levels are consistently (across datasets) associated with aggressiveness vs. non-aggressiveness. Using n-gene weighted voting algorithms, we tested the utility of OGL-identified markers to predict aggressiveness using an independent RNA expression microarray dataset.
Results: We found that an 11 gene signature model, based on expression of genes CASR, ACPP, GADD45B, ADFP, ALDH1A2, ADAM9, CCPG1, HOXC6, IQCK, IGF1 and PAGE 4, predicted aggressive vs. non-aggressive prostate cancer with 86 % accuracy (p=0.0014, based on Fisher's exact test), and was 86% sensitive for detecting aggressive disease. Among our 11 gene signature are genes whose expression levels were previously demonstrated to be associated with high grade and/or aggressive prostate cancer.
Conclusions: Our findings further establish that gene signatures may be predictive of aggressive clinical course following prostatectomy. Further studies of the correlation between expression levels of these 11 genes and clinical outcome are required to establish whether tests based on expression of these genes may be clinically useful in identifying aggressive prostate cancer.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 125, Tuesday Afternoon