African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome
African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome
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DOI：
10.1097/ju.0000000000000193
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发表时间：
2019-08-01
影响因子：
6.6
通讯作者：
Yamoah, Kosj
中科院分区：
文献类型：
--
作者：
Echevarria, Michelle I.;Awasthi, Shivanshu;Yamoah, Kosj
目的：大多数非裔美国男性前列腺癌缺乏ETS （E26转化特异性）家族融合事件（ETS-）。我们的目的是通过研究ETS依赖的基因表达模式，在非裔美国男性中建立临床相关的生物标志物，以确定预测预后的种族特异性基因。材料和方法：两个多中心队列共1427名男性被用于发现和验证种族特异性预测性生物标志物（分别为635名和792名）。我们使用假发现率调整q值来识别种族和ETS依赖基因，这些基因在5年内经历生化复发的非裔美国男性中差异表达。主成分建模与生存分析一起进行，以评估基因面板预测复发的准确性。结果：我们鉴定出3047个基于ETS状态的差异表达基因。在这些基因中，362个以种族特异性方式差异表达（错误发现率0.025或更低）。共有81个基因是种族特异性的，并且在经历生化复发的非裔美国男性中过度表达。最终基因组包括APOD、BCL6、EMP1、MYADM、SRGN和TIMP3。这些基因与5年生化复发相关（HR 1.97, 95% CI 1.27-3.06, p = 0.002），它们仅在非裔美国男性中提高了临床病理变量的预测准确性（60个月时间依赖性AUC 0.72）。结论：为了阐明与非裔美国男性前列腺癌侵袭性相关的生物学特征，我们确定了仅在非裔美国男性中预测早期生化复发的ETS依赖生物标志物。因此，这些依赖ETS的生物标志物代表了该患者群体中侵袭性疾病生物标志物的理想候选者。
Purpose: Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.Materials and Methods: Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.Results: We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95% CI 1.27-3.06, p = 0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).Conclusions: In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.