Background: The incidence and mortality rates of prostate cancer (PCa) are twice as high in African American (AA) than in Caucasian American (CA) men. The molecular alterations associated with this racial disparity have not been fully elucidated. We aim to compare the expression profile of AA and CA men using microarray available data and paraffin-embedded tissues to identify the underlying molecular mechanisms contributing to the disproportionate of PCa among AA men.
Methods: Microarray data of 619 PCa patients, 412 AA and 207 CA, were retrieved from 11 data sets deposited in Gene Expression Omnibus (GEO) database. False discovery rates (FDR) were used for reporting differentially expressed genes and the differentially regulated pathways of these genes were predicted. To validate the microarray data, qPCR analyses were performed in forty paraffin-embedded samples collected from AA and CA men.
Results: Of 362 differential transcripts of array data, TIMP4, LTC4S, SHH, ADIPOQ, and ALOX12 were downregulated (p>0.001) while KLK2, COX5A, AZGP1, AMD1, and ALDH1A3 were upregulated (p>0.001) in PCa AA compared to CA men. qPCR analyses demonstrated that OAT, NKX3, LTC4S, APPL2, TPD52, ALDH, and AMD1 were significantly upregulated (p>0.05) in AA regarding CA men with PCa. Overexpression of OAT, LTC4S, and TPD52 in AA cell lines was confirmed by Western blot analysis. These genes were involved in regulation of cell apoptosis, lipid metabolism, migration, angiogenesis, and response to reactive oxygen species. These transcripts are involved in focal adhesion, PI3K/Akt, EGFR, beta-catenin, and MAPK signaling pathways.
Conclusions: Gene expression data from PCa specimens and microarray suggest that dysregulation of transcripts in PCa of AA compared to CA men may underlie health disparity of PCa. These data might provide new insights into development of reliable diagnostic and prognostic markers of aggressive PCa.
Citation Format: Hamdy Ali, Pei-Yau Lung, Shaimaa Gad, Andrew Sholl, Hamed I. Ali, Jinfeng Zhang, Zakaria Y. Abd Elmageed. Transcriptome-wide profiling identifies novel differential genes associated with health disparity of prostate cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B41.