Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer

Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer
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DOI:
10.3748/wjg.v13.i38.5060
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发表时间:
2007-10-14
影响因子:
4.3
通讯作者:
Wang, Xue-Qing
Wang, Xue-Qing
中科院分区:
医学2区
文献类型:
--
作者:
Wang, He-Ling;Bai, Han;Wang, Xue-Qing

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目的:阐明凋亡蛋白酶激活因子1(Apaf-1)基因与胃癌的关系。方法:收集35例术后癌组织及癌旁正常组织标本。通过半定量 RT-PCR 分析这些样品中 Apaf-1 基因的表达。采用杂合性丢失(LOH)来判断样品中12q22-23域是否存在Apaf-1基因丢失。采用甲基化特异性(MSP)PCR技术分析样本中Apaf-1基因启动子甲基化情况。结果:胃癌组织样本中Apaf-1 mRNA表达率为51%。 D12S346、D12S1706、D12S327、D12S1657 和 D12S393 的 LOH 频率分别为 33%、8%、58%、12% 和 42%。在两个地点发现了 50% 的 LOH,在三个地点发现了 17% 的 LOH。 13例Apaf-1 mRNA表达显着下降(rs=0.487,P=0.003)。胃癌组织样本中Apaf-1启动子甲基化率为49%,癌旁组织样本中Apaf-1启动子甲基化率为23%。 18例胃癌组织中有16例出现启动子甲基化显着,Apaf-1 m RNA表达降低(rs=0.886,P=10-6)。结论:Apaf-1基因在胃癌组织中低表达。 Apaf-1基因启动子的甲基化和12q22-23域的LOH是Apaf-1基因表达和表达改变的主要原因。 (c) 2007 年 WJG。版权所有。
AIM: To elucidate the relationship between apoptotic protease activating factor-1 (Apaf-1) gene and gastric cancer.METHODS: Thirty-five postoperative cancer and adjacent normal tissue samples were collected in the present study. Expression of the Apaf-1 gene in these samples was analyzed by semi-quantitative RT-PCR. Loss of heterozygosity (LOH) was used to determine whether there was loss of Apaf-1 gene in domain of 12q22-23 in the samples. Promoter methylation of Apaf-1 gene in the samples was analyzed by methylation specific (MSP) PCR.RESULTS: The expression of Apaf-1 mRNA in gastric cancer tissue samples was 51%. The LOH frequency of D12S346, D12S1706, D12S327, D12S1657 and D12S393 was 33%, 8%, 58%, 12%, and 42%, respectively. Fifty percent LOH was found at two sites and 17% LOH at three sites. Apaf-1 mRNA expression decreased significantly in 13 cases (rs = 0.487, P = 0.003). The rate of Apaf-1 promoter methylation was 49% in gastric cancer tissue samples and 23% in para-cancerous tissue samples. Promoter methylation occurred significantly in 16 of 18 gastric cancer tissue samples with decreased expression of Apaf-1 m RNA rs = 0.886, P = 10-6).CONCLUSION: The expression of Apaf-1 gene is low in gastric cancer tissues. Methylation of Apaf-1 gene promoter and LOH in domain of 12q22-23 are the main reasons for the expression and altered expression of Apaf-1 gene. (c) 2007 WJG. All rights reserved.