p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer
p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer
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DOI：
10.1016/j.bbrc.2005.11.072
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发表时间：
2006-01-20
影响因子：
3.1
通讯作者：
Nakagawa, M
中科院分区：
文献类型：
--
作者：
Kawamoto, K;Enokida, H;Nakagawa, M
启动子甲基化是细胞周期负调控因子失活的主要机制之一。我们研究了位于RB和p53通路上游的基因p16（INK 4a）和p14（ARF）的甲基化状态是否是人类膀胱癌分期、临床结果和预后的有用生物标志物。应用甲基化特异性PCR（MSP）检测了45例膀胱癌患者（男性34例，女性11例）64例膀胱癌组织中p16（INK 4a）和p14（ARF）基因的甲基化状态。在19例复发性膀胱癌患者中，我们检查了来自其原发性和复发性肿瘤的配对组织样本。通过亚硫酸氢盐DNA测序分析确认代表性样品的甲基化状态。中位随访时间为34.3个月（范围27.0-100.1个月）。在45例患者中，p16（INK 4a）和p14（ARF）甲基化率分别为17.8%和31.1%。p16（1 NKa）和p14（ARF）甲基化的发生率在浸润性（>= pT 2）膀胱癌患者中显著高于表浅性膀胱癌（
Promoter hypermethylation is one of the putative mechanisms underlying the inactivation of negative cell-cycle regulators. We examined whether the methylation status of p16(INK4a) and p14(ARF), genes located upstream of the RB and p53 pathway, is a useful biomarker for the staging, clinical outcome, and prognosis of human bladder cancer. Using methylation-specific PCR (MSP), we examined the methylation status of p16(INK4a) and p14(ARF) in 64 samples from 45 bladder cancer patients (34 males, 11 females). In 19 patients with recurrent bladder cancer, we examined paired tissue samples from their primary and recurrent tumors. The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The median follow-up duration was 34.3 months (range 27.0-100.1 months). The methylation rate for p16(INK4a) and p14(ARF) was 17.8% and 31.1%, respectively, in the 45 patients. The incidence of p16(1NKa) and p14(ARF) methylation was significantly higher in patients with invasive (>= pT2) than superficial bladder cancer (