Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.
Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.
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DOI：
10.1016/s1470-2045(10)70295-3
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发表时间：
2011-03
期刊：
影响因子：
51.1
通讯作者：
Stone, Steven
中科院分区：
文献类型：
--
作者：
Cuzick, Jack;Swanson, Gregory P.;Fisher, Gabrielle;Brothman, Arthur R.;Berney, Daniel M.;Reid, Julia E.;Mesher, David;Speights, V. O.;Stankiewicz, Elzbieta;Foster, Christopher S.;Moller, Henrik;Scardino, Peter;Warren, Jorja D.;Park, Jimmy;Younus, Adib;Flake, Dart D., II;Wagner, Susanne;Gutin, Alexander;Lanchbury, Jerry S.;Stone, Steven
临床局限性前列腺癌的最佳管理提出了独特的挑战，因为它的高度可变的，往往是惰性的自然史。为了预测疾病的侵袭性，临床医生将联合收割机临床参数组合以创建预后模型，但是当前模型的准确性非常有限。有显着的临床需要的生物标志物，提高我们的能力，预测疾病的结果。使用福尔马林固定石蜡包埋的肿瘤样本的RNA定量RT-PCR，我们测量了31个参与细胞周期进展的基因（CCP基因）的表达水平，创建了一个预定义的评分，并评估了其预测疾病结局的能力。在来自美国的366名接受根治性前列腺切除术的患者的回顾性队列中，以及在英国通过经尿道切除术（TURP）诊断并保守治疗的337名临床局限性前列腺癌男性的回顾性队列中，对签名进行了测试。在两个队列中，细胞周期进展特征是高度显著的结局预测因子。直肠癌切除术后，CCP评分预测生化复发的单变量（CCP中一个单位变化的风险比（HR）（加倍）= 1.89; 95% CI（1.54，2.31）χ2 = 34·0，1df，p = 5·6 × 10−9）和多变量分析（HR = 1.74; 95% CI（1.39，2.17）χ2 = 21·65，1df，p = 3·3 ×10−6）。CCP评分和PSA是最佳预测模型中的主导变量，比任何其他临床指标都更有意义。在TURP队列中，CCP评分是预测前列腺癌死亡的主要变量，（HR= 2.92; 95% CI（2.38，3.57）χ2 = 92·7，1df，p = 6.1 × 10−22）和多变量分析（χ2 = 42·2，p = 8·2 × 10 - 11），比所有其他预后因素强得多。在任何情况下，4均没有任何临床参数的CCP评分风险比异质性的显著证据。CCP评分提供了大量关于根治性前列腺切除术后复发风险和经TURP诊断的保守治疗前列腺癌死亡风险的独立信息。总之，这些研究提供了强有力的证据，证明CCP评分是一种高度稳健的预后标志物，在进一步验证后，它可能在确定前列腺癌患者的适当治疗方面发挥核心作用。这项研究由英国癌症研究中心、兰花呼吁、美国国立卫生研究院（SPORE CA 92629）和科赫基金会资助。在Myriad Genetics进行的分子检测。
Optimal management of clinically localized prostate cancer presents unique challenges because of its highly variable and often indolent natural history. To predict disease aggressiveness, clinicians combine clinical parameters to create prognostic models, but the accuracy of current models is very limited. There is significant clinical need for biomarkers that improve our ability to predict disease outcome. Using quantitative RT-PCR on RNA from formalin fixed paraffin-embedded tumour samples, we measured the expression level of 31 genes involved in cell cycle progression (CCP genes), created a predefined score and evaluated its ability to predict disease outcome. The signature was tested in a retrospective cohort of 366 patients from the U.S. who had undergone radical prostatectomy, and in a retrospective cohort of 337 men with clinically localized prostate cancer diagnosed by a transurethral resection (TURP) in the UK and managed conservatively. The cell cycle progression signature was a highly significant predictor of outcome in both cohorts. After prostatectomy the CCP score predicted biochemical recurrence in univariate (Hazard ratio (HR) for a one unit change in CCP (doubling) = 1.89; 95% CI (1.54, 2.31) χ2 = 34·0, 1df, p = 5·6 × 10−9) and multivariate analysis (HR = 1.74; 95% CI (1.39, 2.17) χ2 = 21·65, 1df, p = 3·3 ×10−6). The CCP score and PSA were the dominant variables in the best predictive model and were much more significant than any other clinical measure. In the TURP cohort, the CCP score was the dominant variable for predicting death from prostate cancer in both univariate (HR= 2.92; 95% CI (2.38, 3.57) χ2 = 92·7, 1df, p = 6.1 × 10−22) and multivariate analyses (χ2 = 42·2, p = 8·2 × 10−11), where it was much stronger than all other prognostic factors. In no case 4 was there significant evidence for heterogeneity in the hazard ratio for the CCP score across any clinical parameter. The CCP score provides a substantial amount of independent information about the risk of recurrence after radical prostatectomy and the risk of death in conservatively managed prostate cancer diagnosed by TURP. Taken together, these studies provide strong evidence that the CCP score is a highly robust prognostic marker which, after additional validation, could have a central role in determining appropriate treatment for prostate cancer patients. Study funded by Cancer Research UK, the Orchid Appeal, US National Institutes of Health (SPORE CA92629), and the Koch Foundation. Molecular testing performed at Myriad Genetics.