Prognostic value of polycomb proteins EZH2, BMI1 and SUZ12 and histone modification H3K27me3 in colorectal cancer.

Prognostic value of polycomb proteins EZH2, BMI1 and SUZ12 and histone modification H3K27me3 in colorectal cancer.
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多梳蛋白 EZH2、BMI1 和 SUZ12 以及组蛋白修饰 H3K27me3 在结直肠癌中的预后价值。

DOI:
10.1371/journal.pone.0108265
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Kuppen PJ
Kuppen PJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Benard A;Goossens-Beumer IJ;van Hoesel AQ;Horati H;Putter H;Zeestraten EC;van de Velde CJ;Kuppen PJ

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表观遗传机制的许多变化已被描述在各种类型的肿瘤。为了寻找新的生物标志物,我们研究了多梳组(PcG)蛋白EZH 2,BMI 1和SUZ 12以及相关组蛋白修饰H3 K27 me 3在结直肠癌中的表达。在组织微阵列(TMA)上对PcG蛋白和组蛋白修饰H3 K27 me 3的核表达进行免疫组化(IHC)染色,包括247个肿瘤组织和47个正常组织,并使用半自动Ariol系统进行评分。肿瘤组织显示EZH 2(p = 0.05)和H3 K27 me 3(p<0.001)的表达高于其正常对应物。  联合标记物趋势分析表明,高表达标记物数量的增加与更好的预后相关。在联合标志物分析中,所有四种标志物的高表达与最佳患者生存期和最长无复发生存期相关,与总生存期(p = 0.01,HR 0.42(0.21-0.84))、无疾病生存期(p = 0.007,HR 0.23(0.08-0.67))和局部无复发生存期(p = 0.02,HR 0.30(0.11-0.84))相关。      总之,我们发现PcG蛋白和H3 K27 me 3的表达在我们的研究队列中具有预后价值。与单个标志物相比,通过组合所研究的生物标志物的表达数据来获得更好的患者分层,强调了同时研究多种标志物的重要性。
Numerous changes in epigenetic mechanisms have been described in various types of tumors. In search for new biomarkers, we investigated the expression of Polycomb-group (PcG) proteins EZH2, BMI1 and SUZ12 and associated histone modification H3K27me3 in colorectal cancer. Nuclear expression of PcG proteins and histone modification H3K27me3 were immunohistochemically (IHC) stained on a tissue microarray (TMA), including 247 tumor tissues and 47 normal tissues, and scored using the semi-automated Ariol system. Tumor tissues showed higher expression of EZH2 (p = 0.05) and H3K27me3 (p<0.001) as compared to their normal counterparts. Combined marker trend analyses indicated that an increase in the number of markers showing high expression was associated with better prognosis. High expression of all four markers in the combined marker analyses was correlated with the best patient survival and the longest recurrence-free survival, with overall survival (p = 0.01, HR 0.42(0.21–0.84)), disease-free survival (p = 0.007, HR 0.23(0.08–0.67) and local recurrence-free survival (p = 0.02, HR 0.30(0.11–0.84)). In conclusion, we found that expression of PcG proteins and H3K27me3 showed prognostic value in our study cohort. Better stratification of patients was obtained by combining the expression data of the investigated biomarkers as compared to the individual markers, underlining the importance of investigating multiple markers simultaneously.
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