| [Background]Gastric cancer is one of the most common malignancies in China. Change ofcell junction reduces adhesion, increases invasion, and speeds tumourprogression. Dsg2is a cellular adhesion molecule whose loss plays animportant role in the invasion and metastasis of tumors. And its individual rolein expression pattern and relationship with clinicopathological features ingastric cancer are poorly understood. Recently, some reports have suggestedan association with single nucleotide polymorphisms (SNPs) and gastriccancer, but little is known about role of SNPs of Dsg2gene in gastric cancer.[objective]To study the pattern of Dsg2gene expression and its relationship withclincopathological features in gastric cancer, and to explore the role of SNPs ofDsg2gene rs75530589（C/G）, rs34989303（A/G）, rs12611255（C/T）,rs35762773（C/T）and rs79381523（C/T）in genesis and progression of gastriccancer.[Materials and Methods]1. The expression of Dsg2was detected by immunohistochemistry.1.1Materials:301cases were recruited from the First Affiliated Hospital ofFujian Medical University from January2001to December2010.1.2Methods: All the cases were chosen five different sites of the normalformalin-fixed paraffin-embedded tissues: the normal gastric mucosa tissue,the gastric mucosa cancer, the center of the tumor, the invasiveness frontierand the metastsis lymph nodes. Tissue microarray was made, thenimmunohistochemistry was performed to detect the expression of Dsg2.2. SNPs of Dsg2gene were determined by PCR-LDR.2.1Materials:639unrelated gastric cancer cases were accrued from the First Affiliated Hospital of Fujian Medical University from January2001to December2010.498healthy controls were recruited from routine check-up people whohad no cancer history or family cancer predispositions.2.2Methods: Genomic DNA was extracted from the histologically normalformalin-fixed paraffin-embedded tissues in the distant margin to the tumor andfresh blood of the controls. PCR-based LDR and sequencing were used todetermine the genotypes of rs75530589（C/G）, rs34989303（A/G）,rs12611255（C/T）, rs35762773（C/T） and rs79381523（C/T）.[Results]1. Dsg2was immunolocalised at cellular membrane in normal gastric mucosa.And it was stronger at cell–cell boundaries.2. The expression of Dsg2in normal tissues was significantly higher than ingastric mucosa cancer. Dsg2was immunolocalised at cellular membrane,cytoplasm, or loss.3. The expression of Dsg2in well-differentiated and moderately-differentiatedadenocarcinoma and intestinal type gastric cancer was higher than inmoderately-differentiated and poorly-differentiated adenocarcinoma, mucousadenocarcinoma, singnet-ring cell carcinoma, diffused type gastric cancer.4. Heterogeneous expression of Dsg2was detected in advanced gastriccancer. There was a tendency to decrease in invasive front. And theexpression of lymph node metastasis was higher than of invasive front.5. No association was found between expression of Dsg2and live time ofpatients.6. A significant difference that distribution frequency of Dsg2rs75530589genotype and allele frequency was found in the gastric cancer patients andcontrols. There was a significantly decreased gastric cancer risk (OR(95%CI)=0.6231[0.5124-0.7578]) with C allele. Moreover, a decreased risk wasobserved in men(OR,0.5942). Relations between the differences of thegenotype, allele frequency and clinicopathological parameters of gastriccancer patients were found in lymph node–free, well-differentiated,moderately-differentiated, poorly-differentiated, gastric and intestinal type,infiltrating placenta percreta, breakthrough the whole stomach wall and cardiac part group.7. A significant difference that distribution frequency of Dsg2rs34989303genotype and allele frequency was found in the gastric cancer patients andcontrols. There was a significantly increased gastric cancer risk（OR(95%CI)=1.9177[1.5142-2.4287]）with A allele. Moreover, a increased risk was observedin men(OR,1.7071) and women(OR,2.3400). Relations between thedifferences of the genotype, allele frequency and clinicopathologicalparameters of gastric cancer patients were found in lymph node–free, lymphnode involved, well-differentiated, moderately-differentiated,poorly-differentiated, every Lauren classification, infiltrating deep muscularlayer, infiltrating placenta percreta, breakthrough the whole stomach wall,advanced cancer, cardiac part, gastric body and sinus ventriculi group.8. A significant difference that distribution frequency of Dsg2rs12611255genotype and allele frequency was found in the gastric cancer patients andcontrols. There was a significantly decreased gastric cancer risk（OR(95%CI)=0.3968[0.3265-0.4821]） with C allele. Moreover, a decreased risk wasobserved in men(OR,0.4247) and women(OR,0.2875) with C allele. Relationsbetween the differences of the genotype, allele frequency andclinicopathological parameters of gastric cancer patients were found in lymphnode–free, lymph node involved, moderately-differentiated,poorly-differentiated, every Lauren classification, infiltrating submucous,infiltrating deep muscular layer, infiltrating placenta percreta, breakthrough thewhole stomach wall, advanced cancer, cardiac part, gastric body and sinusventriculi group.9. No significant difference that distribution frequency of Dsg2rs35762773genotype and allele frequency was found in the gastric cancer patients andcontrols. Relations between the differences of the genotype, allele frequencyand clinicopathological parameters of gastric cancer patients were found inmoderately differentiated, infiltrating superficial muscular layer group.10. No significant difference that distribution frequency of Dsg2rs79381523genotype and allele frequency was found in the gastric cancer patients andcontrols.11. No association was found between polymorphisms of rs75530589, rs34989303, rs12611255, rs35762773and rs79381523and live time ofpatients.[Conclusions]1. Dsg2was immunolocalised at cellular membrane in normal gastric mucosa.And it was stronger at cell–cell boundaries. The expression of Dsg2in normaltissues was higher than in cancer, which Dsg2was immunolocalised at cellularmembrane, cytoplasm, or loss.2. The expression of Dsg2in normal tissues was significantly higher than ingastric mucosa cancer, which indicated that down-regulation of Dsg2wasassociated to carcinogenesis of gastric cancer, especially gastric type.3. Heterogeneous expression of Dsg2was detected in advanced gastriccancer, and a downward trend was presented in invasion front, which indicatedthat loss of Dsg2played an important role in the invasion and metastasis oftumors.4. The expression of Dsg2in corresponding lymph node metastatic carcinomawas significantly higher than that in invasion front of primary carcinoma, whichsuggested that reexpression of Dsg2could promote formation of metastaticmass.5. It should not be deemed that the expression of Dsg2affect prognosis of GC.6. Dsg2rs75530589, rs34989303, rs12611255polymorphism may beassociated with the risk of developing gastric cancer, and influence lymphnode metastasis, differentiation, histological typing, invasive ability andlocation of gastric cancer.7. Dsg2rs35762773polymorphism may be no associated with the risk ofdeveloping gastric cancer, but may be influence location and infiltrate depth.8. Dsg2rs79381523polymorphism may be no associated with the risk ofdeveloping gastric cancer.9．It should not be deemed that SNPs of Dsg2affect prognosis of gastriccancer. |
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