CDH17表达及其SNPs在胃癌发生发展中的意义

Significance of CDH17 expression and its single nucleotide polymorphisms in oncogenesis and progression of gastric carcinoma

目的:探讨CDH17表达与胃癌临床病理学特征的关系及其SNPs与胃癌遗传易感性的关系。方法:制作模拟胃癌侵袭转移动态的组织芯片,免疫组织化学SP法检测CDH17蛋白的表达,PCR-LDR技术检测CDH17基因2个SNPs位点rs2514813和rs3214050的多态性并行测序验证。结果:胃癌CDH17表达上调与组织学分化程度呈正相关(P<0.01);肠型胃癌表达高于弥漫型胃癌;随着侵袭过程的进展,黏膜层、肿瘤中央区、侵袭前沿区胃癌的CDH17表达水平呈下降趋势;CDH17表达与胃癌术后生存时间未见明显相关(P=0.209)。胃癌CDH17基因SNP位点rs3214050等位基因C、T频率及CC、CT和TT的基因型频率与对照组相比差异有统计学意义(P<0.01),携带等位基因T的胃癌患者术后生存时间长于CC基因型(P<0.01)。rs2514813位点基因型与等位基因频率与对照组相比无显著性差异(P>0.05)。结论:CDH17表达升高与胃癌腺样结构的维持及进展相关,rs3214050位点为T等位基因者患胃癌风险低且预后好,提示该位点与中国福建汉族人群胃癌的遗传易感性及预后有关。

Objective： To explore the relationship of CDH17 expression with clinico-pathological features and the correlation be- tween the single nucleotide polymorphisms （SNPs） of CDH17 gene and genetic susceptibility of gastric carcinoma （GC）. Methods： A tissue microarray was performed to simulate the dynamic process of invasion and metastasis of GC. Immunohistochemical staining was performed to detect the expression of CDH17 protein, and PCR-based LDR was performed to detect the 2 SNP loci （rs2514813 and rs3214050） genotypes of CDH17 gene. Results： The expression of CDH17 protein in GC was more significantly up-regulated and greatly increased in the intestinal type than in the diffuse type. The expression of CDH17 protein in GC was positively correlated with the histological grading （P〈0.01） and was not associated with the survival （P=0.209）. With the progression of the cancer invasion, the expression of CDH17 protein in GC showed a downtrend from the gastric mucosa layer to the invasive front edge. The frequencies of the C and T alleles and the CC, CT, and TT genotypes at the CDH17 rs3214050 locus between the GC patients and the control groups were significantly different （P〈0.01）. However, no significant differences were observed at rs2514813 （P〉0.05）. The individuals with the T al- leles had longer survival time than those with the CC genotype （P〈0.01）. Conclusion： The up-regulation of CDH17 expression is in- volved in the maintenance of histological phenotype and progression of GC. Individuals with T alleles at the CDH17 rs3214050 locus have decreased risk of GC and had better prognosis （OR=0.762, 95%CI：0.619-0.937）, thereby suggesting that screening for these alleles would help with the assessment of genetic susceptibility and prognosis of GC in the Fujian population.