Mena表达及SNPs与胃癌遗传易感性及预后

Relationship of Mena expression and SNP polymorphisms with the susceptibility and prognosis of gastric cancer

目的：探讨Mena表达与胃癌侵袭转移的相关性及SNPs与胃癌遗传易感性的关系。方法：制作模拟胃癌侵袭转移过程的组织芯片，免疫组化染色检测Mena蛋白的表达。PCR—LDR技术检测Mena基因5个SNPs位点多态性并行测序验证。结果：胃腺癌中Mena表达上调，肠型与混合型胃癌高于弥漫型，并与胃癌侵袭转移负相关，Mena高表达者预后好。Mena基因SNP位点rs3795443的188例对照组等位基因A、G的频率分别为91．0％和9．0％，胃癌病例组等位基因A、c的频率为82．4％和17．6％；AA、A／G和GG的基因型频率在对照组分别为81．9％、18．1％和0，而在病例组为68．35％、28．09％和3．56％，差异具有统计学意义（OR=2．1489，95％CI：1．4607～3．1613，P〈0．01）。5个SNPs位点的基因型和等位基因频率与胃癌术后生存时间均无明显相关性。结论：胃癌Mena表达升高，组织学类型的维持以及侵袭转移与其表达密切相关，高表达者预后好。MenaSNPrs3795443位点携带等位基因G的GG和A／G基因型个体的胃癌患病风险提高，提示检测该位点基因型有助于评估胃癌的遗传易感性。

Objective：To investigate the correlation ot lviena protein cxp, c~,, with genetic susceptibility in gastric cancers （GC）. Methods：A tissue microarray that simulates the invasion and metastasis process of GC was created, and immunohistochemistry was performed to detect the expression of Mena protein. The Mena gene 5 SNP loci geno- types of 188 healthy people and 389 GC patients were assayed using PCR-based LDR analysis. Results： The expression of Mena pro- tein in GC was significantly upregulated and greatly increased in the intestinal-type and mixed-type GC than that in the diffuse-type and was negatively related to the invasion and metastasis of GC. Patients with Mena overexpression had better prognosis. The frequen- cies of the A and G alleles, as well as the AA, AG, and GG genotypes, at the Mean SNP rs3795443 locus were significantly different be- tween patients with gastric carcinoma and the control groups （OR=2.1489,95%CI 1.4607 - 3.1613, P〈0.01）. The frequencies of these five Mena gene SNP loci were not significantly related with the survival of patients with gastric carcinoma. Conclusion ： The upregula- tion of Mena expression is involved in maintaining the histological phenotype, invasion, metastasis, and prognosis of gastric adenocarci- noma. Individuals with GG and AG genotypes at the Mena rs3795443 locus have increased risk of gastric carcinoma, which suggests that screening for this genotype would be helpful in assessing the genetic susceptibility of gastric carcinoma.