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中国胃癌患者PAI-1基因5'-侧翼区的基因不稳定与CpG甲基化

Genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene in Chinese patients with gastric cancer.

作者信息

Liu J, Li X, Yu N, Yang Y-Q, Li X, Ye Z-Y, Li J-C

机构信息

Institute of Cell Biology, Zhejiang University, Hangzhou, China.

出版信息

Genet Mol Res. 2012 Aug 29;11(3):2899-908. doi: 10.4238/2012.May.18.11.

DOI:10.4238/2012.May.18.11
PMID:22653645
Abstract

We explored a possible correlation of genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene with clinicopathologic features of gastric cancer in Chinese patients and looked for molecular markers for diagnosing gastric tumor development. Microsatellite instability and loss of heterozygosity of the PAI-1 gene locus D7S515, D7S471 and pai-1 in 50 specimens of gastric cancer and relevant pericancerous tissues were detected by PCR-single strand conformation polymorphism (PCR-SSCP) with sliver staining. Methylation-specific PCR was used to detect CpG methylation in the 5'-flanking region of the PAI-1 gene. Microsatellite instability was significantly more common in the negative than in the positive serosa infiltration group of gastric cancer (42.86 vs 2.33%). The frequency of microsatellite instability was significantly lower in the cases with lymph node metastasis than in those without metastasis (18.18 vs 2.56%); however, it was significantly higher in the low differentiation group than that in the middle or high differentiation groups (21.05 vs 0.00%). CpG methylation in the 5'-flanking region of the PAI-1 gene did not differ significantly. Microsatellite instability and loss of heterozygosity of the PAI-1 gene apparently regulates the development of gastric cancer through different pathways. Microsatellite instability could be used as a molecular marker for the development of gastric cancer. CpG methylation in the 5'-flanking region of the PAI-1 gene appears not to be involved in the development of gastric cancer.

摘要

我们探讨了中国胃癌患者中PAI - 1基因5'侧翼区的基因不稳定与CpG甲基化和胃癌临床病理特征之间的可能相关性,并寻找诊断胃癌发生发展的分子标志物。采用PCR - 单链构象多态性(PCR - SSCP)银染法检测50例胃癌及相关癌旁组织中PAI - 1基因位点D7S515、D7S471和pai - 1的微卫星不稳定性及杂合性缺失。采用甲基化特异性PCR检测PAI - 1基因5'侧翼区的CpG甲基化。微卫星不稳定性在胃癌阴性浆膜浸润组显著高于阳性组(42.86%对2.33%)。微卫星不稳定性在有淋巴结转移的病例中显著低于无转移的病例(18.18%对2.56%);然而,在低分化组显著高于中分化或高分化组(21.05%对0.00%)。PAI - 1基因5'侧翼区的CpG甲基化无显著差异。PAI - 1基因的微卫星不稳定性和杂合性缺失显然通过不同途径调控胃癌的发生发展。微卫星不稳定性可作为胃癌发生发展的分子标志物。PAI - 1基因5'侧翼区的CpG甲基化似乎不参与胃癌的发生发展。

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