Abstract 2210: The study of age and race genetic signatures of prostate cancer with formalin fixed paraffin embedded (FFPE) samples
Authors: Sharad Shashwat , Nousome Darryl , Chesnut Gregory T. , Li Hua 
Published: June 2022

Objectives: Diagnosis with prostate cancer (PCa) at younger age is a serious challenge in Military Health System. PCa onset at younger age is more likely to be aggressive in African American (AA) population. Also, application of formalin fixed paraffin embedded (FFPE) tissue in RNA based study was significantly hindered due to poor quality/quantity of RNA in archived pathology slides. This study is aimed to examine age/race associated gene signatures in military cohort with high representation of AA and younger population in FFPE samples for potential genetic mechanisms of health disparities and broaden tissue sample availability.

Methods: A cohort of 41 Caucasian American (CA) and 20 AA non-familial PCa patients from the biospecimen bank of CPDR, WRNMMC were used. Specimens donated by radical prostatectomy patients who provided written consent and protocols approved by Institutional Review Boards. Total RNA was extracted from tumor and the adjacent normal epithelium of whole-mount FFPE tissue of matched specimens. Differential gene expression, in tumor versus normal tissues, between younger and older AA and CA patients were analyzed by NanoString using a customized CodeSet of 151 probes. The panel designed to detect 135 target transcripts, compiled from 34 genes implicated/associated with PCa progression, 27 PCa specific gene fusions, 25 cancer-associated genes, and 5 genes encoding ETS-family of transcription factors. The 27 over-expressed genes and 17 under-expressed genes in PCa were included as comparison to matched, benign epithelium. Additionally, 5 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 AA older (66-73 years) and younger (42-58 years) as well as CA older and younger PCa patients with moderate Gleason score (3+3 and 3+4) sum were identified. After controlling for false discovery rates, panel of nine genes (ANXA2, C-MYC, VEGFR1, ERG, NPY, PSMA/FOLH1, TWIST1, MAOA, MYCN) uniquely associated with age/race were identified. Tumor vs normal ratios of ANXA2 and C-MYC expression in prostate tumors of older and younger patients were significantly enhanced. We found a clear association of VEGFR1 gene expression with CA young and c-MYC gene with AA young PCa.

Conclusions: Using age/race as endpoint, we identified ANXA2, c-MYC and VEGFR1 as age and race associated PCa gene. Our findings highlight distinct racial and age-related differences and addresses the clinical utility of available genetic tests across old and young AA and CA men, which needs to be further validated in lager cohort. Further, our study also highlighted the utilization of FFPE tissue for NanoString assay and subsequent genetic signature analyses.

Citation Format: Shashwat Sharad, Darryl Nousome, Gregory T. Chesnut, Hua Li. The study of age and race genetic signatures of prostate cancer with formalin fixed paraffin embedded (FFPE) samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2210.