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

Dysregulated gene expression predicts tumor aggressiveness in African-American prostate cancer patients.
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DOI:
10.1038/s41598-018-34637-8
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发表时间:
2018-11-05
期刊:
影响因子:
4.6
通讯作者:
Abd Elmageed ZY
Abd Elmageed ZY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ali HEA;Lung PY;Sholl AB;Gad SA;Bustamante JJ;Ali HI;Rhim JS;Deep G;Zhang J;Abd Elmageed ZY

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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.
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