Expression And SNPs Of CLDN23 In Gastric Carcinoma

Objective:To investigate the relationship between SNPs and the expression of CLDN23 with the Biological behavior in gastric cancer.Methods:A cohort of 215 archival formalin-fixed paraffin-embedded tissues of gastric cancer cases and 197 blood samples of healthy controls were accrued from the First Affiliated Hospital of Fujian Medical University from October 1993 to September 2007.PCR-based LDR and sequencing were used to determine the genotypes of Rs12153,Rs1060106 and Rs11249884 of CLDN23 gene. 194 cases were collected from archival formalin-fixed paraffin-embedded tissues. Tissue microarray was made, then immunohistochemistry was performed to detect the expression of claudin-23 protein.Results:1. Compared with normal gastric epithelial,the expression of claudin-23 in glandular epithelium of intestinal metaplasia was significantly located in the Membrane.2.Compared with normal gastric mucosa,gastric cancer tissue showed a variety of aberrant expression of claudin-23 from membranous expression changed to cytoplasmic expression.3.The degree of aberrant expression of claudin-23 in cancer tissue in mucosa was correlated with gender,sex,tumor differentiation, invasion depth, lymph node metastasis(P<0.001).4.The differentiation in gastric cancer tissue was related with the expression of claudin-23.The lower aberrant expression was found in the higher differentiation in gastric cancer tissue(P<0.001).5.The degree of aberrant expression of claudin-23 was intensified compared cancer tissue in mucosa to that in the invasive front of gastric carcinomas, while the degree of aberrant expression of claudin-23 in lymph node metastasis was weaker than those in the invasive front(P<0.05).6.The survival rate after surgical treatment of patients with claudin-23 severe expression of tumor tissue in mucosa and the center of tumor was lower than the rate of those with claudin-23 mild expression (P<0.01).7 . No significant difference that distribution frequency of CLDN23-Rs12153 genotype and allele frequency was found in the gastric cancer patients and controls(P>0.05). The frequencies of the genotypes was significantly related with differentiated degree, invasion depth in gastric carcinomas cases(P<0.01), The survival rate after surgical treatment of patients with genotypes CC of Rs12153 locus was higher than these with CG genotype(P<0.01).8 . No significant difference that distribution frequency of CLDN23-Rs1060106 genotype and allele frequency was found in the gastric cancer patients and controls(P>0.05). The frequencies of the genotypes was significantly related with differentiated degree, invasion depth in gastric carcinomas cases(P<0.01), The survival rate after surgical treatment of patients with genotypes TT and CT of Rs1060106 locus was higher than these with CC genotype.9.No significant difference that distribution frequency of CLDN23- Rs11249884 genotype and allele frequency was found in the gastric cancer patients and controls(P>0.05). The frequencies of the genotypes was significantly related with differentiated degree, invasion depth in gastric carcinomas cases(P<0.01), The survival rate after surgical treatment of patients with genotypes AA of Rs11249884 locus was higher than these with AG genotype(P<0.05). 10 . Linkage equilibrium was observed among Rs12153,Rs1060106 and Rs11249884.There was a statistic significance in distribution of possible haplotypes among Rs12153,Rs1060106 and Rs11249884.No association was found between GG-CC-GG,CG-CT-AG,CC-TT-AA genotype constructed by Rs12153,Rs1060106 and Rs11249884 and live time of patients.Conclusions:1.The aberrant expression of claudin-23 is involved in carcinogenesis,invasion and metastasis in gastric carcinoma.2.Claudin-23 aberrant expression of tumor tissue in mucosa and the center of tumor is related with prognosis in gastric carcinoma.3.CLDN23 Rs12153 polymorphism is not associated with susceptibility of gastric cancer in Chinese population, but may influence differentiation, invasion depth and Clinical stage of gastric cancer. The survival rate after surgical treatment of patients with genotypes CC of Rs12153 locus was higher than these with CG genotype.4.CLDN23 Rs1060106 polymorphism is not associated with susceptibility of gastric cancer in Chinese population, but may influence differentiation, invasion depth of gastric cancer. The survival rate after surgical treatment of patients with genotypes TT and CT of Rs1060106 locus was higher than these with CC genotype.5.CLDN23 Rs11249884 polymorphism is not associated with susceptibility of gastric cancer in Chinese population, but may influence differentiation, invasion depth and Clinical stage of gastric cancer. The survival rate after surgical treatment of patients with genotypes AA of Rs11249884 locus was higher than these with AG genotype.