Abstract: PD71-12
Sources of Funding: DOD

Introduction

We reported functional driver genes and network interaction of race specific and differentially expressed genes by use of bioinformatics among a large population of African American men (AAM) and European American men (EAM) (Powell, I et al 2013, Cancer Epid Bio Prev.). Within this network we subsequently identified biological pathways reported elsewhere that activate directly or indirectly the androgen receptor. We will present these pathways from our interactive network.

Methods

In our initial microarray analysis from formalin fixed radical prostatectomy specimens, we examined 227 genes from 517 genes associated with PCa showing significantly greater expression in PCa from AAM and EAM, and a subset of these genes was identified by bioinformatics and the network from Ingenuity Pathways to be functionally interrelated and driver genes. Genes associated with inflammatory cytokines (blue) and lipid metabolism (yellow) were expressed among AAM and EAM respectively. SEE FIGURE1

Results

Biological Pathways identified in our functional driver gene network that activate the androgen receptor: 1. ALOX12/ALOX15 ?TNF ?IL6/IL1B (Fairfax et al,2010) 2. IL1B? MAPK ? IL8 (Tsai et al 2009) 3. IL6 ?mediators AKt, MAPK and STAT3? activated androgen receptor (Jia et al 2004) 4. IL8 binds to CXCR ½ receptors at the cell surface and activate the androgen receptors through multiple mediators of cell signaling in the PCa cell (Waugh and Wilson 2008).

Conclusions

These biomarker pathways may be useful markers in diagnosing aggressive prostate cancer and in the development of targeted biologic therapy. Further analyses may reveal additional pathways.

Funding

DOD