High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer
High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer
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高CpG岛甲基化表型与胃癌淋巴结转移和预后相关
DOI：
10.1111/j.1349-7006.2011.02129.x
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发表时间：
2012-01-01
期刊：
影响因子：
5.7
通讯作者：
He, Yu-Long
中科院分区：
文献类型：
--
作者：
Chen, Hua-Yun;Zhu, Bao-He;He, Yu-Long
研究发现，胃癌组织中启动子区CpG岛甲基化程度较高。CpG岛甲基化表型（CIMP）定义了胃癌亚组中多个启动子CpG岛位点的一致甲基化。然而，CIMP与胃癌淋巴结转移的关系尚不清楚。我们的研究旨在描述CIMP在淋巴结转移中的作用。对120例患者的临床标本进行分析，并采用PCR方法检测ALX 4、TMEFF 2、CHCHD 10、IGFBP 3和NPR 1 5个基因的甲基化状态。我们通过实时RT-PCR测量了这五个基因的mRNA水平。采用毛细管电泳和实时荧光定量PCR分别检测微卫星不稳定性和幽门螺杆菌感染状况。这五个基因的DNA甲基化与各自mRNA的低表达相关。以CIMP为因变量，CIMP高的胃癌有淋巴结转移、病理分型、病理转移和病理TNM分期高的趋势。微卫星不稳定性与H. pylori状态对预后无显著预测作用。CIMP阳性胃癌患者的生存率明显低于CIMP阴性或CIMP阴性胃癌患者（P < 0.001）。我们的研究结果表明，CIMP状态与胃癌淋巴结转移之间存在相关性，CIMP高是一个独立的预后因素。（Cancer Sci 2012; 103：73-79）
Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor. (Cancer Sci 2012; 103: 73-79)