Alterations of global histone H4K20 methylation during prostate carcinogenesis.

Alterations of global histone H4K20 methylation during prostate carcinogenesis.
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DOI:
10.1186/1471-2490-12-5
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发表时间:
2012-03-13
期刊:
影响因子:
2
通讯作者:
Ellinger J
Ellinger J
中科院分区:
医学4区
文献类型:
--
作者:
Behbahani TE;Kahl P;von der Gathen J;Heukamp LC;Baumann C;Gütgemann I;Walter B;Hofstädter F;Bastian PJ;von Ruecker A;Müller SC;Rogenhofer S;Ellinger J

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全球组蛋白修饰已涉及各种肿瘤实体的进展。我们的研究旨在评估组蛋白4赖氨酸20(H4 K20 me 1 -3)在前列腺癌(PCA)癌变不同阶段的整体甲基化水平。使用组织微阵列在患有临床局限性PCA(n = 113)、非恶性前列腺疾病(n = 27)、转移性原发性PCA(mPCA,n = 30)和去势抵抗性PCA(CRPC,n = 34)的患者中评估总体H4 K20甲基化水平。进行免疫组织化学以评估H4 K20甲基化水平的总体水平。相似比例的正常、PCA和mPCA前列腺组织显示强H4 K20 me 3染色。CRPC组织分析显示,与其他前列腺组织相比,H4 K20 me 1和H4 K20 me 2的免疫染色水平最弱。H4 K20 me 2甲基化水平表明除了正常前列腺与PCA组织之外,在检查的组织中存在显著差异。H4 K20 me 1可将CRPC与其他前列腺组织区分开来。H4 K20 me 1与淋巴结转移显著相关,H4 K20 me 2与Gleason评分显著相关。然而,H4 K20甲基化水平未能预测根治性前列腺切除术后PSA复发。H4 K20甲基化水平构成了前列腺癌癌变动态过程的有价值的标志物。
Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3) at different stages of prostate cancer (PCA) carcinogenesis. Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113), non-malignant prostate disease (n = 27), metastatic hormone-naive PCA (mPCA, n = 30) and castration-resistant PCA (CRPC, n = 34). Immunohistochemistry was performed to assess global levels of H4K20 methylation levels. Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy. H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.
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