CDH17表达及其SNPs在胃癌发生发展中的意义
Significance of CDH 17expression and its single nucleotide polymorphisms in oncogenesis and progression of gastric carcinoma
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摘要: 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。Abstract: 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.
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Keywords:
- Cadherin- 17 /
- gastric carcinoma /
- invasion /
- metastasis /
- immunohistochemistry /
- single nucleotide polymorphism
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期刊类型引用(5)
1. 吴璐璐,尹婷婷,李佳. 胃癌患者Bmi-1、CDH17、胃蛋白酶原检测及与临床病理特征的关系. 临床血液学杂志. 2021(10): 697-702 . 百度学术
2. 韩峥,田霞,黄晓东,朱庆曦,谭洁,刘蒙. 下调CDH17基因对那可丁耐药性人胃癌细胞作用的分析. 基因组学与应用生物学. 2017(05): 1692-1696 . 百度学术
3. 于建华,王运良,潘晓琳. CDH17和LRP1B基因多态性与一氧化碳中毒后迟发性脑病的相关性. 中国实用神经疾病杂志. 2017(12): 18-22 . 百度学术
4. 林晶,江小杰,蔡清河. CDH17与胃癌关系的研究进展. 医学综述. 2017(11): 2166-2170 . 百度学术
5. 杨健. COLPH3、PI3K/Akt/mTOR信号通路与胃癌发生、发展关系. 中国医学创新. 2017(08): 138-140 . 百度学术
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