Dysregulated gene expression predicts tumor aggressiveness in African-American prostate cancer patients

Abstract

Molecular mechanisms underlying the health disparity of prostate cancer (PCa) have not been fully determined. In this study, we applied bioinformatic approach to identify and validate dysregulated genes associated with tumor aggressiveness in African American (AA) compared to Caucasian American (CA) men with PCa. We retrieved and analyzed microarray data from 619 PCa patients, 412 AA and 207 CA, and we validated these genes in tumor tissues and cell lines by Real-Time PCR, Western blot, immunocytochemistry (ICC) and immunohistochemistry (IHC) analyses. We identified 362 differentially expressed genes in AA men and involved in regulating signaling pathways associated with tumor aggressiveness. In PCa tissues and cells, NKX3.1, APPL2, TPD52, LTC4S, ALDH1A3 and AMD1 transcripts were significantly upregulated (p < 0.05) compared to normal cells. IHC confirmed the overexpression of TPD52 (p = 0.0098) and LTC4S (p < 0.0005) in AA compared to CA men. ICC and Western blot analyses additionally corroborated this observation in PCa cells. These findings suggest that dysregulation of transcripts in PCa may drive the disparity of PCa outcomes and provide new insights into development of new therapeutic agents against aggressive tumors. More studies are warranted to investigate the clinical significance of these dysregulated genes in promoting the oncogenic pathways in AA men.

Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications

“…In PCA tissues, NKX3.1, APPL2, TPG5, ALDH1A3, and AMD1 transcripts are significantly upregulated. Immunohistochemistry studies confirmed the overexpression of TPD52 and LTC45 in AAM compared to CaM prostate cancer [323].…”

Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition

“…E006AA cells are also available from Millipore Sigma but recent report revealed that E006AA-hT were 86% closer to renal cell carcinoma [32]. These cells were cultured as we previously described [57]. Briefly, cells were maintained in either DMEM or RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin (Life Technologies Corp., Grand Island, NY, USA).…”

“…RC77T/E PCa cells and RC77N/E normal prostate cells were provided by Dr. J.S. Rhim (Uniformed Services University) and maintained as described [57]. All cells were maintained at 37 • C and 5% CO 2 and tested for mycoplasma every six months.…”

“…Conventional PCR was also performed to optimize and guarantee the specificity of the ITGA2 primer. The fold change of gene expression in the two set of experiments was calculated compared to β-actin and 5SrRNA by comparing Ct method as described [57].…”

Common pathways and functional profiles reveal underlying patterns in Breast, Kidney and Lung cancers

“…It is widely known that specific mutations are able to induce cancer [4] and that many genes and microRNAs are deregulated in tumor tissues [5]. The study of the genomic characteristics of each cancer has lead to the establishment of diverse subtypes defined by the different mutations they include and with a very heterogeneous response to drugs and survival [6]. To address the differences between these subtypes, many bioinformatic approaches have been developed, such as CancerSubtypes, a R package aimed to retrieve all the main computational methods for cancer subtypes identification and analysis [7].…”