Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome
Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome
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DOI：
10.1038/sj.onc.1207800
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发表时间：
2004-08-05
期刊：
影响因子：
8
通讯作者：
Cooper, CS
中科院分区：
文献类型：
--
作者：
Foster, CS;Falconer, A;Cooper, CS
E2 F转录因子，包括EM，直接调节EZH 2的表达。最近，EZH 2基因的过表达已经涉及人前列腺癌的发展。在组织微阵列研究中，我们现在表明，高水平的核E2 F3的表达发生在高比例（98/147，67%）的人前列腺癌，但在非肿瘤性前列腺上皮细胞中是一个罕见的事件，这表明E2 F3过表达在前列腺癌发生中的作用。与未检测到E2 F3表达的前列腺癌患者相比，表现出可检测到的细胞核E2 F3表达的前列腺癌患者的总生存率（P=0.0022）和病因特异性生存率（P=0.0047）较差。当根据在其前列腺癌中鉴定的EM阳性核的最大百分比（高达20、21- 40%等）对患者进行分层时，E2 F3染色与总生存率（P=0.0014）和病因特异性生存率（P=0.0004）的死亡风险之间的相关性越来越显著。多变量分析选择E2 F3表达作为预测总生存率（未分层P=0.0103，分层P=0.0086）和病因特异性生存率（未分层P=0.0288，分层P=0.0072）的独立因素。当这些结果与EZH 2和E2 F3控制蛋白pRB的已发表数据一起考虑时，我们得出结论，pRB-E2 F3-EZH 2控制轴可能在调节个体人前列腺癌的侵袭性中具有关键作用。
E2F transcription factors, including EM, directly modulate expression of EZH2. Recently, overexpression of the EZH2 gene has been implicated in the development of human prostate cancer. In tissue microrarray studies we now show that expression of high levels of nuclear E2F3 occurs in a high proportion (98/147, 67%) of human prostate cancers, but is a rare event in non-neoplastic prostatic epithelium suggesting a role for E2F3 overexpression in prostate carcinogenesis. Patients with prostate cancer exhibiting immunohistochemically detectable nuclear E2F3 expression have poorer overall survival (P=0.0022) and cause-specific survival (P=0.0047) than patients without detectable E2F3 expression. When patients are stratified according to the maximum percentage of EM-positive nuclei identified within their prostate cancers (up to 20, 21-40%, etc.), there is an increasingly significant association between E2F3 staining and risk of death both for overall survival (P=0.0014) and for cause-specific survival (P=0.0004). Multivariate analyses select E2F3 expression as an independent factor predicting overall survival (unstratified P=0.0103, stratified P=0.0086) and cause-specific survival (unstratified P=0.0288, stratified P=0.0072). When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer.