Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer
Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-13-1105
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发表时间：
2014-09-01
影响因子：
11.5
通讯作者：
Homma, Yukio
中科院分区：
文献类型：
--
作者：
Fujimura, Tetsuya;Takahashi, Satou;Homma, Yukio
目的：雄激素和雌激素基因、信号转导细胞和干细胞样细胞在前列腺癌中起重要作用。这项研究旨在通过识别这些前列腺癌相关基因来预测临床失败。实验设计：我们开发了预测临床失败的模型，使用来自46名训练集的活检样本和30名治疗未获治疗的前列腺癌伴骨转移患者的独立验证集。采用激光捕获显微解剖技术分别采集癌组织和间质组织。我们分析了临床失败与雄激素受体(AR)及其相关基因(APP、Fox家族、TRIM 36、Oct1和ACSL 3)、干细胞样分子(Klf4、c-Myc、Oct3/4和Sox2)、雌激素受体(ER)、Her2、PSA和CRP.的mRNA表达之间的关系。结果：Logistic分析显示，预测前列腺特异性抗原(PSA)复发的Logistic分析结果显示，Sox2、Her2和CRP在癌细胞中的表达，AR和ERA在间质细胞中的表达，以及临床参数，在两组中的曲线下面积(AUC)均为1.0。我们确定了10个影响癌症特异性生存(CSS)的预后因素：癌细胞中Oct1、TRIM36、Sox2和c-Myc的表达；间质细胞中AR、KLF4和ERA的表达；以及PSA、Gleason评分和疾病程度。在这些因素的基础上，根据存在的因素的数量将患者分为有利风险组、中等风险组和不良风险组。三组患者的5年生存率分别为90%、32%和12%，而在验证组分别为75%、48%和0%。结论：雄激素和雌激素信号成分和干细胞标志物的表达水平是预测预后的有力工具。(C)2014年AACR。
Purpose: Genes of androgen and estrogen signaling cells and stem cell-like cells play crucial roles in prostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes.Experimental Design: We developed models to predict clinical failure using biopsy samples from a training set of 46 and an independent validation set of 30 patients with treatment-naive prostate cancer with bone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection. We analyzed the association between clinical failure andmRNAexpression of the following genes androgen receptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell-like molecules (Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP.Results: Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under the curve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERa expression in stromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS): Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERa expression in stromal cells; and PSA, Gleason score, and extent of disease. Onthe basis of these factors, patients were divided into favorable-, intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3 groups were 90%, 32%, and12% in the training set and 75%, 48%, and0% in the validation set, respectively.Conclusions: Expression levels of androgen-and estrogen signaling components and stem cell markers are powerful prognostic tools. (C) 2014 AACR.