Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer.
Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer.
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DOI：
10.1186/1471-2407-14-977
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发表时间：
2014-12-18
期刊：
影响因子：
3.8
通讯作者：
Leung HY
中科院分区：
文献类型：
--
作者：
Rajan P;Stockley J;Sudbery IM;Fleming JT;Hedley A;Kalna G;Sims D;Ponting CP;Heger A;Robson CN;McMenemin RM;Pedley ID;Leung HY
虽然前列腺癌（PCa）的化疗可以提高患者的生存率，但有些肿瘤对化疗具有耐药性。肿瘤分子谱可能有助于确定药物作用机制和确定潜在的预后生物标志物。我们对接受多西他赛化疗和雄激素剥夺治疗（ADT）的晚期未经化疗的前列腺癌患者的治疗前和治疗后前列腺活检组织进行了体内转录组分析，旨在确定药物作用机制并确定预后生物标志物。在开始多西他赛和ADT治疗前和治疗后约22周，对4例患者的活检组织进行RNA测序（RNA-Seq）。使用TopHat和途径富集分析鉴定了处理对之间的基因融合产物和差异调节基因。查询公开可用的数据集，以对使用cBioportal鉴定的基因特征进行生存分析。在化疗前和化疗后，在患者中鉴定了许多基因组重排，包括TMPRSS 2/ERG融合和3种涉及ETS家族转录因子的新基因融合。总的来说，基因表达分析显示，化疗后活检的575个基因中至少有2倍的差异表达。其中，通路分析确定了一组7个基因（ADAM 7、FAM 72 B、BUB 1B、CCNB 1、CCNB 2、TTK、CDK 1），包括一个细胞周期相关基因，这些基因在多西他赛和ADT治疗后受到差异调节。使用cBioportal询问MSKCC-前列腺肿瘤基因组计划数据集，我们观察到肿瘤患者的无病生存期显著降低，这些肿瘤患者表现出上述7个基因组的基因表达改变（p = 0.015）。在这里，我们报告了第一个“实时”体内基于RNA-Seq的转录组分析临床PCa，来自多西他赛化疗加ADT治疗患者的治疗前和治疗后TRUSS引导活检。我们确定了一个化疗驱动的PCa转录谱，其中包括细胞周期进程的重要正调控下调。在高危前列腺癌患者中也已确定7个基因签名生物标志物组具有预后价值。未来的前瞻性研究是必要的，以评估该面板的临床价值。本文的在线版本（doi：10.1186/1471-2407-14-977）包含补充材料，可供授权用户使用。
Although chemotherapy for prostate cancer (PCa) can improve patient survival, some tumours are chemo-resistant. Tumour molecular profiles may help identify the mechanisms of drug action and identify potential prognostic biomarkers. We performed in vivo transcriptome profiling of pre- and post-treatment prostatic biopsies from patients with advanced hormone-naive prostate cancer treated with docetaxel chemotherapy and androgen deprivation therapy (ADT) with an aim to identify the mechanisms of drug action and identify prognostic biomarkers. RNA sequencing (RNA-Seq) was performed on biopsies from four patients before and ~22 weeks after docetaxel and ADT initiation. Gene fusion products and differentially-regulated genes between treatment pairs were identified using TopHat and pathway enrichment analyses undertaken. Publically available datasets were interrogated to perform survival analyses on the gene signatures identified using cBioportal. A number of genomic rearrangements were identified including the TMPRSS2/ERG fusion and 3 novel gene fusions involving the ETS family of transcription factors in patients, both pre and post chemotherapy. In total, gene expression analyses showed differential expression of at least 2 fold in 575 genes in post-chemotherapy biopsies. Of these, pathway analyses identified a panel of 7 genes (ADAM7, FAM72B, BUB1B, CCNB1, CCNB2, TTK, CDK1), including a cell cycle-related geneset, that were differentially-regulated following treatment with docetaxel and ADT. Using cBioportal to interrogate the MSKCC-Prostate Oncogenome Project dataset we observed a statistically-significant reduction in disease-free survival of patients with tumours exhibiting alterations in gene expression of the above panel of 7 genes (p = 0.015). Here we report on the first “real-time” in vivo RNA-Seq-based transcriptome analysis of clinical PCa from pre- and post-treatment TRUSS-guided biopsies of patients treated with docetaxel chemotherapy plus ADT. We identify a chemotherapy-driven PCa transcriptome profile which includes the down-regulation of important positive regulators of cell cycle progression. A 7 gene signature biomarker panel has also been identified in high-risk prostate cancer patients to be of prognostic value. Future prospective study is warranted to evaluate the clinical value of this panel. The online version of this article (doi:10.1186/1471-2407-14-977) contains supplementary material, which is available to authorized users.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
23.4
作者：
Omlin, Aurelius;Pezaro, Carmel;de Bono, Johann
通讯作者：
de Bono, Johann
影响因子：
51.1
作者：
Gravis, Gwenaelle;Fizazi, Karim;Soulie, Michel
通讯作者：
Soulie, Michel
影响因子：
51.1
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
通讯作者：
Stone, Steven
影响因子：
158.5
作者：
Petrylak, DP;Tangen, CM;Crawford, ED
通讯作者：
Crawford, ED