Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients.
Genomic, epigenomic, and transcriptomic signatures of prostate cancer between African American and European American patients.
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DOI：
10.3389/fonc.2023.1079037
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发表时间：
2023
影响因子：
4.7
通讯作者：
Rhie, Suhn K.
中科院分区：
文献类型：
--
作者：
Stevens, Claire;Hightower, Alexandria;Buxbaum, Sarah G.;Falzarano, Sara M.;Rhie, Suhn K.
关键词：
前列腺癌是美国男性第二大常见癌症，并且该疾病存在很大的种族差异。具体而言，非洲裔美国人 (AA) 患者的发病率和死亡率比欧洲裔美国人 (EA) 患者高出 60%，此外，前列腺肿瘤的级别和分期也较高。为了缩小这两个人群临床结果之间的差距，对造成这种差异的遗传和分子特征进行了表征。在过去的十年中，利用分子和功能测定结合下一代测序或微阵列，开发了来自不同种族群体的前列腺肿瘤样本的概况。对前列腺肿瘤样本的基因组、表观基因组和转录组谱进行比较全基因组分析，发现了潜在的种族特异性突变、拷贝数改变、DNA 甲基化和基因表达模式。在这项研究中，我们回顾了 20 多项已发表的研究，这些研究检验了上述 AA 和 EA 前列腺癌患者种族差异的分子贡献。审查的基因组研究揭示了 AA 患者与 EA 患者中突变、缺失、扩增、重复或融合基因的差异性富集。常见的基因组改变包括 FOXA1、KMT2D、SPOP、MYC、PTEN、TP53、ZFHX3 和 TMPRSS2-ERG 融合体的突变或拷贝数改变。回顾性表观基因组研究发现，AA 和 EA 患者之间 PMEPA1、RARB、SNRPN 和 TIMP3 基因启动子附近的 CpG 位点甲基化存在差异。最后，审查的转录组学研究确定了 AA 和 EA 患者之间失调的基因（例如 CCL4、CHRM3、CRYBB2、CXCR4、GALR1、GSTM3、SPINK1）和信号通路。最常见的失调途径涉及免疫和炎症反应以及神经活性配体信号传导。总体而言，我们观察到，在 AA 和 EA 前列腺癌患者之间评估的基因组、表观基因组和转录组改变在不同研究之间存在差异，凸显了使用不同方法和样本量的影响。报道的基因组、表观基因组和转录组改变不仅揭示了肿瘤发生的分子机制，而且还为研究人员和临床医生提供了宝贵的资源，以识别新的生物标志物和治疗方式，以改善 AA 和 EA 患者之间临床结果的差异。
Prostate cancer is the second most common cancer in men in the United States, and racial disparities are greatly observed in the disease. Specifically, African American (AA) patients have 60% higher incidence and mortality rates, in addition to higher grade and stage prostate tumors, than European American (EA) patients. In order to narrow the gap between clinical outcomes for these two populations, genetic and molecular signatures contributing to this disparity have been characterized. Over the past decade, profiles of prostate tumor samples from different ethnic groups have been developed using molecular and functional assays coupled with next generation sequencing or microarrays. Comparative genome-wide analyses of genomic, epigenomic, and transcriptomic profiles from prostate tumor samples have uncovered potential race-specific mutations, copy number alterations, DNA methylation, and gene expression patterns. In this study, we reviewed over 20 published studies that examined the aforementioned molecular contributions to racial disparities in AA and EA prostate cancer patients. The reviewed genomic studies revealed mutations, deletions, amplifications, duplications, or fusion genes differentially enriched in AA patients relative to EA patients. Commonly reported genomic alterations included mutations or copy number alterations of FOXA1, KMT2D, SPOP, MYC, PTEN, TP53, ZFHX3, and the TMPRSS2-ERG fusion. The reviewed epigenomic studies identified that CpG sites near the promoters of PMEPA1, RARB, SNRPN, and TIMP3 genes were differentially methylated between AA and EA patients. Lastly, the reviewed transcriptomic studies identified genes (e.g. CCL4, CHRM3, CRYBB2, CXCR4, GALR1, GSTM3, SPINK1) and signaling pathways dysregulated between AA and EA patients. The most frequently found dysregulated pathways were involved in immune and inflammatory responses and neuroactive ligand signaling. Overall, we observed that the genomic, epigenomic, and transcriptomic alterations evaluated between AA and EA prostate cancer patients varied between studies, highlighting the impact of using different methods and sample sizes. The reported genomic, epigenomic, and transcriptomic alterations do not only uncover molecular mechanisms of tumorigenesis but also provide researchers and clinicians valuable resources to identify novel biomarkers and treatment modalities to improve the disparity of clinical outcomes between AA and EA patients.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
17.1
作者：
Ateeq B;Tomlins SA;Laxman B;Asangani IA;Cao Q;Cao X;Li Y;Wang X;Feng FY;Pienta KJ;Varambally S;Chinnaiyan AM
通讯作者：
Chinnaiyan AM
影响因子：
16.6
作者：
Bernasocchi T;El Tekle G;Bolis M;Mutti A;Vallerga A;Brandt LP;Spriano F;Svinkina T;Zoma M;Ceserani V;Rinaldi A;Janouskova H;Bossi D;Cavalli M;Mosole S;Geiger R;Dong Z;Yang CG;Albino D;Rinaldi A;Schraml P;Linder S;Carbone GM;Alimonti A;Bertoni F;Moch H;Carr SA;Zwart W;Kruithof-de Julio M;Rubin MA;Udeshi ND;Theurillat JP
通讯作者：
Theurillat JP
影响因子：
28.4
作者：
Dess, Robert T.;Hartman, Holly E.;Spratt, Daniel E.
通讯作者：
Spratt, Daniel E.
影响因子：
6.6
作者：
Banez, Lionel L.;Sun, Leon;Castanos-Velez, Esmeralda
通讯作者：
Castanos-Velez, Esmeralda