KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for Prostate-Specific Antigen-Relapse Following Radical Prostatectomy.
目前，有很少能够获得的预后因素来预测去势治疗前列腺癌后肿瘤的再次复发，并且没有有效的治疗选择可供参考。表观基因调控能够触发前列腺癌的转移和引发雄激素非依赖性前列腺癌。组蛋白赖氨酸脱甲基酶(KDMs)是一种可以去除抑制和激活组蛋白标记的表观酶。KDM5家族成员能够去除组蛋白H3赖氨酸4的二甲基化（一种激活标记），致使它们成为下调肿瘤抑制的潜在成员，这表明它们的活性能够抑制癌基因。我们在两个独立的根治性前列腺癌切除术组（共822例前列腺肿瘤），采用免疫组织化学系统性的研究了KDM5C的表达模式。KDM5C标记核的阳性表达，与降低前列腺特异性抗原的无复发生存率显著相关。我们的研究表明KDM5C核表达是独立的预后指标。最引人注目的是，KDM5C核表达对无进展生存率的预后价值是专门针对Gleason评分为7的肿瘤组。另外，下调KDM5C表达后导致体外前列腺癌细胞的生长阻滞，并诱导调控几个增殖相关的基因，我们的数据表明：KDM5C参与前列腺癌细胞的增殖调控，并有可能成为新的治疗前列腺癌的治疗靶点；此外，KDM5C的过表达是前列腺切除术后治疗失败和肿瘤复发的一个独立的、新的预测指标。

Currently, few prognostic factors are available to predict the emergence of castration-resistant prostate cancer and no curative options are available. Epigenetic gene regulation has been shown to trigger prostate cancer metastasis and androgen independence. Histone lysine demethylases (KDMs) are epigenetic enzymes that can remove both repressive and activating histone marks. KDM5 family members are capable of removing the histone H3 lysine 4 dimethylation eactivating mark, rendering them potential players in the down-regulation of tumor suppressors and suggesting that their activity could repress oncogenes. Here, we systematically investigated KDM5C expression patterns in two in-dependent radical prostatectomy cohorts (822 prostate tumors in total) by immunohistochemistry.Positive nuclear KDM5C staining was significantly associated with a reduced prostate-specific antigen relapse-free survival. Our study confirmed that nuclear KDM5C expression is an independent prognostic parameter. Most strikingly, the prognostic value of nuclear KDM5C expression for progression-free survival was exclusively pronounced for the Gleason group 7. In addition, KDM5C knockdown resulted in growth retardation of prostate cancer cells in vitro and induced regulation of several proliferation-associated genes. Our data indicate that KDM5C is functionally involved in proliferation control of prostate cancer cells and might represent a novel attractive therapy target. Moreover, overexpression of KDM5C is an independent new predictive marker for therapy failure as determined by biochemical recurrence in patients after prostatectomy. (Am J Pathol 2014, -:1e 8; http://dx.doi.org/10.1016/.jajpath.2014.05.022 )

KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for Prostate-Specific Antigen-Relapse Following Radical Prostatectomy.
这个英文标题翻译的一直很拗口，请各位老师们，指导

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