Department of Urology, University Hospital Bonn, Bonn, Germany.
Anticancer Res. 2012 Mar;32(3):879-86.
BACKGROUND/AIM: To determine the role of global histone H3K9 and H4K20 methylation levels as prognostic parameters in patients with renal cell cancer (RCC).
Global histone methylation levels were investigated in 193 RCC (including 142 clear cell (cc), 31 papillary (p), 10 chromophobe (ch) and 10 sarcomatoid (s) RCC), 10 oncocytomas and 30 benign renal specimens.
Histone modifications were mostly similar in the different histological subtypes (p>0.05); significant differences were observed for ccRCC vs. pRCC and pRCC vs. sRCC. Comparing the global H3K9 methylation levels of benign renal tissue with RCC H3K9me1 (histone H3 lysine 9 mono-methylation) (p<0.001), H3K9me2 (histone H3 lysine 9 di-methylation) (p=0.001) and H3K9me3 (histone H3 lysine 9 tri-methylation) (p<0.001) was significantly over-expressed in benign renal tissue. H3K9 and H4K20 methylation levels were positively correlated to pT-stage (p<0.005) and grading (p<0.05). In localized RCC (n=144), H3K9me1 levels showed a significant correlation with progression-free survival in the univariate model (p=0.034).
Global histone methylation levels may help to identify RCC patients with poor prognosis.
背景/目的:确定组蛋白 H3K9 和 H4K20 整体甲基化水平作为预测肾细胞癌(RCC)患者预后的参数的作用。
在 193 例 RCC(包括 142 例透明细胞(cc)、31 例乳头状(p)、10 例嫌色细胞(ch)和 10 例肉瘤样(s)RCC)、10 例嗜酸细胞瘤和 30 例良性肾组织标本中,研究了组蛋白甲基化水平。
不同组织学亚型的组蛋白修饰大多相似(p>0.05);ccRCC 与 pRCC 及 pRCC 与 sRCC 之间存在显著差异。与良性肾组织中的 RCC H3K9me1(组蛋白 H3 赖氨酸 9 单甲基化)相比,H3K9me1(p<0.001)、H3K9me2(组蛋白 H3 赖氨酸 9 二甲基化)(p=0.001)和 H3K9me3(组蛋白 H3 赖氨酸 9 三甲基化)(p<0.001)在良性肾组织中明显过表达。H3K9 和 H4K20 甲基化水平与 pT 分期(p<0.005)和分级(p<0.05)呈正相关。在局限性 RCC(n=144)中,H3K9me1 水平在单变量模型中与无进展生存期有显著相关性(p=0.034)。
组蛋白整体甲基化水平可能有助于识别预后不良的 RCC 患者。