Application of histone modification in the risk prediction of the biochemical recurrence after radical prostatectomy

Application of histone modification in the risk prediction of the biochemical recurrence after radical prostatectomy
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DOI:
10.1038/aja.2009.81
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发表时间:
2010-03-01
影响因子:
2.9
通讯作者:
Li, Dong
Li, Dong
中科院分区:
医学2区
文献类型:
--
作者:
Zhou, Li-Xin;Li, Tao;Li, Dong

文献摘要

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组蛋白修饰在癌症发生和发展中的作用尚不清楚。在此,我们研究了各种组蛋白修饰与根治性前列腺切除术(RP)后生化复发风险预测的关系。采用免疫组织化学结合组织芯片技术对169例原发性前列腺切除术组织样本进行组蛋白3赖氨酸4二甲基化(H3K4diMe)、三甲基化(H3K4triMe)、赖氨酸36三甲基化(H3K36triMe)、组蛋白4赖氨酸20三甲基化(H4K20triMe)和组蛋白3赖氨酸9乙酰化(H3K9Ac)的评价。采用递归划分分析(RPA)对数据进行分析。通过对根治性前列腺切除术患者的整体组蛋白修饰分析,我们发现H3K4triMe可以预测低级别前列腺癌(Gleason评分= 7)的生化复发风险,H4K20triMe和H3K9Ac伴术前前列腺特异性抗原(PSA)水平也可以预测RP术后生化复发风险。结合Gleason评分和术前PSA水平,组蛋白H3和H4的乙酰化和甲基化可预测RP术后前列腺癌的生化复发。
The role of histone modifications in the development and progression of cancer remains unclear. Here, we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy (RP). Histone 3 lysine 4 dimethylation (H3K4diMe), trimethylation (H3K4triMe), lysine 36 trimethylation (H3K36triMe), histone 4 lysine 20 trimethylation (H4K20triMe) and acetylation of histome 3 lysine 9 (H3K9Ac) were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis (RPA) was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy, we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer (Gleason score = 7), H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen (PSA) level could also predict the risk of the biochemical recurrence after RP. In combination with the Gleason score and pre-operation PSA level, the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.