Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, TX, USA.
Department of Radiobiological Applications, Nuclear Research Center, Atomic Energy Authority, Cairo, Egypt.
Sci Rep. 2018 Nov 5;8(1):16335. doi: 10.1038/s41598-018-34637-8.
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.
前列腺癌（PCa）健康差异的潜在分子机制尚未完全确定。在这项研究中，我们应用生物信息学方法来鉴定和验证与非裔美国（AA）男性相比，白种人（CA）男性的 PCa 肿瘤侵袭性相关的失调基因。我们从 619 名 PCa 患者、412 名 AA 和 207 名 CA 中检索和分析了微阵列数据，并通过实时 PCR、Western blot、免疫细胞化学（ICC）和免疫组织化学（IHC）分析在肿瘤组织和细胞系中验证了这些基因。我们确定了 362 个在 AA 男性中差异表达的基因，这些基因涉及调节与肿瘤侵袭性相关的信号通路。在 PCa 组织和细胞中，NKX3.1、APPL2、TPD52、LTC4S、ALDH1A3 和 AMD1 的转录本与正常细胞相比显著上调（p<0.05）。IHC 证实了 TPD52（p=0.0098）和 LTC4S（p<0.0005）在 AA 中比 CA 男性的过度表达。ICC 和 Western blot 分析进一步证实了这一观察结果在 PCa 细胞中。这些发现表明，PCa 中转录本的失调可能导致 PCa 结局的差异，并为开发针对侵袭性肿瘤的新治疗药物提供了新的见解。需要进一步的研究来探讨这些失调基因在促进 AA 男性致癌途径中的临床意义。
