偶数缺失同源盒 1 在前列腺癌中经常发生高甲基化，并可预测 PSA 复发。
Even-skipped homeobox 1 is frequently hypermethylated in prostate cancer and predicts PSA recurrence.
机构信息
Department of Urology, University of Wisconsin School of Medicine and Public Health, 7037, Wisconsin Institutes for Medical Research, 1111 Highland Avenue, Madison, WI 53792, USA.
出版信息
Br J Cancer. 2012 Jun 26;107(1):100-7. doi: 10.1038/bjc.2012.216. Epub 2012 May 17.
BACKGROUND
DNA methylation is an important epigenetic mechanism in prostate cancer (PCa) progression. Given the role of even-skipped homeobox 1 (EVX1) in the regulation of multiple genes during embryogenesis, we postulated that EVX1 methylation is altered in PCa progression.
METHODS
Bisulphite sequencing and quantitative MethyLight were used to assess methylation in human prostate epithelial cells, four PCa cell lines, liver, lung, spleen, kidney, 35 paired tumour and tumour-associated benign tissues, and 11 normal prostate tissues. Prostate cancer cell lines were treated with 5-azacytidine (AzaC) or trichostatin A (TSA), and expression of EVX1 transcript and variants was assessed by qPCR. Hypermethylation was compared with clinicopathological features in a validation set of 58 patients using microarray.
RESULTS
Even-skipped homeobox 1 hypermethylation was observed in all four PCa cell lines and 57% of tumours. High-grade tumours exhibited increased methylation compared with intermediate-grade tumours. Even-skipped homeobox 1 expression was induced in PCa cell lines after treatment with AzaC or TSA. In the validation set, 83% of tumours were hypermethylated and hypermethylation was associated with worse recurrence-free survival.
CONCLUSION
In this first evaluation of EVX1 methylation in human cancer, EVX1 is one of the most commonly hypermethylated genes observed in PCa and predicted treatment failure in moderate risk patients.
背景
DNA 甲基化是前列腺癌（PCa）进展中的一种重要的表观遗传机制。鉴于偶数跳过同源盒 1（EVX1）在胚胎发生过程中对多个基因的调控作用，我们推测 EVX1 甲基化在 PCa 进展中发生了改变。
方法
采用亚硫酸氢盐测序和定量 MethyLight 方法评估人前列腺上皮细胞、四种 PCa 细胞系、肝、肺、脾、肾、35 对肿瘤及肿瘤相关良性组织和 11 份正常前列腺组织中的甲基化情况。用 5-氮杂胞苷（AzaC）或曲古抑菌素 A（TSA）处理前列腺癌细胞系，并用 qPCR 评估 EVX1 转录本和变体的表达。在 58 例患者的验证组中，使用微阵列比较高甲基化与临床病理特征的关系。
结果
在所有四种 PCa 细胞系和 57%的肿瘤中观察到偶数跳过同源盒 1 高甲基化。与中等级别肿瘤相比，高级别肿瘤表现出更高的甲基化。PCa 细胞系经 AzaC 或 TSA 处理后，EVX1 表达被诱导。在验证组中，83%的肿瘤发生高甲基化，高甲基化与无复发生存不良相关。
结论
在人类癌症中首次评估 EVX1 甲基化，EVX1 是 PCa 中观察到的最常发生高甲基化的基因之一，预测中危患者治疗失败。
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