Epigenetic signature of Gleason score and prostate cancer recurrence after radical prostatectomy.
Epigenetic signature of Gleason score and prostate cancer recurrence after radical prostatectomy.
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DOI：
10.1186/s13148-016-0260-z
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发表时间：
2016
影响因子：
5.7
通讯作者：
Stanford JL
中科院分区：
文献类型：
--
作者：
Geybels MS;Wright JL;Bibikova M;Klotzle B;Fan JB;Zhao S;Feng Z;Ostrander EA;Lin DW;Nelson PS;Stanford JL
确定临床局限性前列腺癌(PCa)复发风险最高的患者亚组仍然具有挑战性，需要更好的预后标记物。Gleason评分是预测PCa侵袭性和预后的最佳指标。在目前的研究中，我们根据高Gleason评分肿瘤和低Gleason评分肿瘤生成表观遗传学特征，并评估其预测前列腺癌根治术后复发的能力。来自癌症基因组图谱的全基因组DNA甲基化数据(TCGA；通过对比高(8-10)和低( = 6)Gleason评分肿瘤的患者，使用弹性网络方法生成表观遗传学特征。然后在523名接受根治性前列腺切除术的临床局限性疾病患者的队列中测试了这一特征。取自原发肿瘤的样本用于DNA甲基化和mRNA表达谱分析。确诊后平均随访8年，观察PCa复发情况。表观遗传特征包括52个差异甲基化的CpG位点。在测试队列中，签名与较差的无复发生存率相关(风险比每25%增加 = 1.78；95%可信区间1.48，2.16)。与单独的临床病理参数相比，该签名显著改善了前列腺癌复发的曲线下面积，特别是在被诊断为格里森评分7的肿瘤患者中(0.64vs.0.76，P = 1.34E−4)。Gleason 3 + 4和4 + 3肿瘤患者的结果具有可比性。基因集浓缩分析表明，高水平的信号与细胞周期增殖相关基因的表达增加，而雄激素反应基因的表达减少。这份报告表明，在前列腺肿瘤细胞中测量的DNA甲基化模式可以预测前列腺癌的侵袭性。表观遗传学特征可能具有改善预后的临床实用价值，特别是在Gleason评分为7的中等肿瘤患者。本文的在线版本(doi：10.1186/s131480160260-z)包含补充材料，授权用户可以使用。
Identifying the subset of patients with clinically localized prostate cancer (PCa) at the highest risk of recurrence remains challenging, and better prognostic markers are needed. Gleason score is the best predictor of PCa aggressiveness and prognosis. In the present study, we generated an epigenetic signature based on high versus low Gleason score tumors and evaluated its ability to predict recurrence after radical prostatectomy. Genome-wide DNA methylation data from The Cancer Genome Atlas (TCGA; no. of patients = 333) and the elastic net method were used to generate an epigenetic signature by contrasting patients with high (8–10) versus low (≤6) Gleason score tumors. The signature was then tested in a cohort of 523 patients with clinically localized disease who had radical prostatectomy. Samples taken from the primary tumor were used for DNA methylation and mRNA expression profiling. Patients were followed for PCa recurrence on average for 8 years after diagnosis. The epigenetic signature includes 52 differentially methylated CpG sites. In the testing cohort, the signature was associated with poorer recurrence-free survival (hazard ratio per 25 % increase = 1.78; 95 % confidence interval 1.48, 2.16). The signature significantly improved the area under the curve (AUC) for PCa recurrence compared to clinical-pathological parameters alone, particularly among patients diagnosed with Gleason score 7 tumors (0.64 vs. 0.76, P = 1.34E−4). Results were comparable for patients with Gleason 3 + 4 and those with 4 + 3 tumors. Gene Set Enrichment Analysis showed that higher levels of the signature were associated with increased expression of genes related to cell cycle proliferation and decreased expression of androgen-responsive genes. This report shows evidence that DNA methylation patterns measured in prostate tumor cells are predictive of PCa aggressiveness. The epigenetic signature may have clinical utility to improve prognostication particularly in patients with intermediate Gleason score 7 tumors. The online version of this article (doi:10.1186/s13148-016-0260-z) contains supplementary material, which is available to authorized users.
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影响因子：
12.3
作者：
Lou S;Lee HM;Qin H;Li JW;Gao Z;Liu X;Chan LL;Kl Lam V;So WY;Wang Y;Lok S;Wang J;Ma RC;Tsui SK;Chan JC;Chan TF;Yip KY
通讯作者：
Yip KY
前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
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：
50.3
作者：
Mazor T;Pankov A;Johnson BE;Hong C;Hamilton EG;Bell RJA;Smirnov IV;Reis GF;Phillips JJ;Barnes MJ;Idbaih A;Alentorn A;Kloezeman JJ;Lamfers MLM;Bollen AW;Taylor BS;Molinaro AM;Olshen AB;Chang SM;Song JS;Costello JF
通讯作者：
Costello JF