CDH17表达及其SNPs在胃癌发生发展中的意义

目的：探讨CDH 17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CDH 17蛋白的表达，PCR-LDR技术检测CDH 17基因2 个SNPs位点rs 2514813和rs 3214050 的多态性并行测序验证。结果：胃癌CDH 17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CDH 17表达水平呈下降趋势；CDH 17表达与胃癌术后生存时间未见明显相关（P = 0.209）。 胃癌CDH 17基因SNP 位点rs 3214050 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）。 rs 2514813 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：CDH 17表达升高与胃癌腺样结构的维持及进展相关，rs 3214050 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。

Significance of CDH 17expression and its single nucleotide polymorphisms in oncogenesis and progression of gastric carcinoma

Objective:To explore the relationship of CDH17expression with clinico-pathological features and the correlation be-tween the single nucleotide polymorphisms (SNPs) of CDH 17gene and genetic susceptibility of gastric carcinoma (GC). Methods:Atissue microarray was performed to simulate the dynamic process of invasion and metastasis of GC. Immunohistochemical staining was performed to detect the expression of CDH 17protein, and PCR- based LDR was performed to detect the2 SNP loci (rs 2514813 and rs 3214050) genotypes of CDH 17gene. Results: The expression of CDH 17protein in GC was more significantly up- regulated and greatly increased in the intestinal type than in the diffuse type. The expression of CDH17protein 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 CDH 17protein 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 CDH 17rs 3214050 locus between the GC patients and the control groups were significantly different (P<0.01). However, no significant differences were observed at rs 2514813 (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 CDH 17expression is in-volved in the maintenance of histological phenotype and progression of GC. Individuals with T alleles at the CDH 17rs 3214050 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.