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商业性前列腺癌预后基因表达检测提供了种族特异性风险的矛盾估计。

Commercial Gene Expression Tests for Prostate Cancer Prognosis Provide Paradoxical Estimates of Race-Specific Risk.

机构信息

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

出版信息

Cancer Epidemiol Biomarkers Prev. 2020 Jan;29(1):246-253. doi: 10.1158/1055-9965.EPI-19-0407. Epub 2019 Nov 22.

Abstract

BACKGROUND

Commercial gene expression signatures of prostate cancer prognosis were developed and validated in cohorts of predominantly European American men (EAM). Limited research exists on the value of such signatures in African American men (AAM), who have poor prostate cancer outcomes. We explored differences in gene expression between EAM and AAM for three commercially available panels recommended by the National Comprehensive Cancer Network for prostate cancer prognosis.

METHODS

A total of 232 EAM and 95 AAM patients provided radical prostatectomy specimens. Gene expression was quantified using NanoString for 60 genes spanning the Oncotype DX Prostate, Prolaris, and Decipher panels. A continuous expression-based risk score was approximated for each. Differential expression, intrapanel coexpression, and risk by race were assessed.

RESULTS

Clinical and pathologic features were similar between AAM and EAM. Differential expression by race was observed for 48% of genes measured, although the magnitudes of expression differences were small. Coexpression patterns were more strongly preserved by race group for Oncotype DX and Decipher than Prolaris. Poorer prognosis was estimated in EAM versus AAM for Oncotype DX ( < 0.001), whereas negligible prognostic differences were predicted between AAM and EAM using Prolaris or Decipher ( > 0.05).

CONCLUSIONS

Because of observed racial differences across three commercial gene expression panels for prostate cancer prognosis, caution is warranted when applying these panels in clinical decision-making in AAM.

IMPACT

Differences in gene expression by race for three commercial panels for prostate cancer prognosis indicate that further study of their effectiveness in AAM with long-term follow-up is warranted.

摘要

背景

商业基因表达谱用于预测前列腺癌的预后,这些基因表达谱是在以欧洲裔美国人(EAM)为主的队列中开发和验证的。在非洲裔美国人(AAM)中,这些基因表达谱的应用价值有限,因为 AAM 的前列腺癌预后较差。我们研究了三种商业化的基因表达谱在预测前列腺癌预后方面,在 EAM 和 AAM 之间的基因表达差异,这三种基因表达谱均被美国国家综合癌症网络推荐用于前列腺癌的预后评估。

方法

共纳入 232 名 EAM 和 95 名 AAM 患者,收集他们的根治性前列腺切除术标本。使用 NanoString 技术对跨越 Oncotype DX Prostate、Prolaris 和 Decipher 三个基因表达谱的 60 个基因进行了基因表达定量分析。为每个基因表达谱近似了一个基于表达的连续风险评分。评估了种族间的差异表达、面板内共表达和风险。

结果

AAM 和 EAM 患者的临床和病理特征相似。种族间差异表达的基因占测量基因的 48%,尽管表达差异的幅度较小。Oncotype DX 和 Decipher 基因表达谱的种族间更能保持共表达模式,而 Prolaris 则不然。Oncotype DX 预测 EAM 的预后比 AAM 差(<0.001),而 Prolaris 或 Decipher 预测 AAM 和 EAM 之间的预后差异可以忽略不计(>0.05)。

结论

由于在三个商业基因表达谱中观察到了与前列腺癌预后相关的种族差异,因此在 AAM 患者的临床决策中应用这些基因表达谱时应谨慎。

影响

三种商业基因表达谱在预测前列腺癌预后方面的种族差异表明,需要进一步研究这些基因表达谱在 AAM 中的有效性,并进行长期随访。

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本文引用的文献

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