凋亡蛋白酶激活因子-1基因在胃癌中的表达及表达改变的理论依据。
Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer.
作者信息
Wang He-Ling, Bai Han, Li Yan, Sun Jun, Wang Xue-Qing
机构信息
Department of Gastroenterology, Shengjing Hospital Affiliated to China Medical University, Shenyang110004, Liaoning Province, China.
出版信息
World J Gastroenterol. 2007 Oct 14;13(38):5060-4. doi: 10.3748/wjg.v13.i38.5060.
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 mRNA 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.
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
本研究收集了35例术后癌组织及癌旁正常组织样本。采用半定量逆转录聚合酶链反应（RT-PCR）分析这些样本中Apaf-1基因的表达。通过杂合性缺失（LOH）检测来确定样本中12q22-23区域是否存在Apaf-1基因缺失。采用甲基化特异性（MSP）PCR分析样本中Apaf-1基因的启动子甲基化情况。
结果
胃癌组织样本中Apaf-1 mRNA的表达率为51%。D12S346、D12S1706、D12S327、D12S1657和D12S393的LOH频率分别为33%、8%、58%、12%和42%。在两个位点发现50%的LOH，在三个位点发现17%的LOH。13例样本中Apaf-1 mRNA表达显著降低（rs=0.487，P=0.003）。胃癌组织样本中Apaf-1启动子甲基化率为49%，癌旁组织样本中为23%。在18例Apaf-1 mRNA表达降低的胃癌组织样本中，有16例发生了显著的启动子甲基化（rs=0.886，P=10⁻⁶）。
结论
胃癌组织中Apaf-1基因表达较低。Apaf-1基因启动子甲基化及12q22-23区域的LOH是导致Apaf-1基因表达及表达改变的主要原因。
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