PD16-12: Age and Race specific gene signature: An independent predictor of prostate cancer in racially diverse military cohort of African and Caucasian American patients

Shashwat Sharad*, Bethesda, MD, Darryl Nousome, Frederick, MD, Gregory Chesnut, Hua Li, Bethesda, MD

Introduction: Age and Racial disparities in prostate cancer (PCa) is a serious challenge and the PCa mortality rates are nearly three times higher in African American (AA) men younger than age 65 than White Caucasian American (CA) men. Young age prostate cancer is more likely to be an aggressive cancer commonly seen in AA population.  The objective of this study is to examine the age and racial disparities associated gene signatures for disease progression, patient stratification and targeted therapeutic options.

Methods: Specimens collected from radical prostatectomy patients (41 CA and 20 AA) who provided written consent under protocols (#393738, #GT90CM/385525 and #908925) approved by the Institutional Review Boards of the Walter Reed National Military Medical Center (WRNMMC) and the Uniformed Services University of the Health Sciences (USUHS).  We used a cohort of non-familial PCa patients of AA and CA origin. Total RNA was extracted from tumor, and adjacent normal epithelium of formalin-fixed-paraffin-embedded (FFPE) specimens by Laser capture microdissection (LCM). Differential gene expression in tumor versus normal tissues between young and old AA and CA patients were analyzed by NanoString using a customized CodeSet of 151 probes sets. The panel was designed to detect 135 target transcripts, which were compiled from 34 genes implicated in or associated with prostate cancer progression, 27 prostate cancer specific gene fusions, 25 cancer associated genes, five genes encoding the ETS-family of transcription factors and genes over-expressed (27) or under-expressed (17) in PCa compared to matched benign epithelium. In addition, five prostate stroma or epithelium specific genes were selected as control and 11 housekeeping genes were included for biological normalization.

Results: The differentially expressed genes related to tumor-normal differences between the old (66–73 yrs) and young (42–58 yrs) AA and CA prostate cancer patients with Gleason (3+3 and 3+4) were identified.  After controlling for false discovery rates, we identified a panel of nine genes (ANXA2, C-MYC, VEGFR1, ERG, NPY, PSMA/FOLH1, TWIST1, MAOA, MYCN) uniquely associated with the age and race. The tumor vs. normal ratios of ANXA2 and c-MYC expression in prostate tumors of old and young patients were found to be significant. We found a clear association of VEGFR1 gene expression with CA young and c-MYC gene with AA young PCa. Our study highlights the potential of using FFPE tissue as a source for the analysis of prognostic biomarkers for PCa.

Conclusions: An unmet challenge in PCa is the identification of biomarkers for early detection of aggressive disease. Effective biomarkers with high specificity will provide early treatment options for high-risk patients. Using Age and Race as the endpoint, we identified ANXA2, c-MYC and VEGFR1 as age and race associated PCa gene which needs to be further validated in the lager cohort. Our findings clearly highlight distinct racial and age-related differences and addresses the clinical utility of available genetic tests across old and young AA and CA men.

Source of Funding: This study was supported by CPDR, USUHS, HU0001-10-2-0002.