Significance Of Expression And SNPs Of14-3-3σ In Occurrence And Development Of Gastric Carcinoma

Background:14-3-3is a highly conserved proteins family that widely found in eukaryotic cells,and play a variety of physiological and pathological functions. It controls the cellcycle、the cell growth、differentiation、survival、apoptosis and migration. One14-3-3isoform,14-3-3σ, is associated with occurrence and development of various tumors.Objective:1. To explore the significance of14-3-3σ gene expression with clinicopathologicalfeatures in gastric cancer.2. To investgate the role of SNPs of14-3-3σ gene rs11542705、 rs1883660ingenesis and progression of gastric cancer.Methods:1. Tissue microarray was made:278cases after surgery opertation in the FirstAffiliated Hospital of Fujian Medical University from January2001to December2010have the complete following-up data. All the cases were chosen five differentsites of the normal formalin-fixed paraffin-embedded tissues: the normal gastricmucosa tissue，the gastric cancer tissue at mucous layer、the center of the tumor、theinvasiveness frontier and the metastsis lymph nodes.49of cases were chosen anothersite of intestinal metaplasia mucosa. Three pieces of tissues were drawn at each sitethen tissue microarray was made.2. The expression of14-3-3σ was detected by immunohistochemistry.3. Two SNPs of14-3-3σ gene were explorded by PCR-LDR method:200cases ofgastric carcinoma after surgery opertation in the First Affiliated Hospital of FujianMedical University from January2001to December2010were collected,200health contorls were recruited form routine check-up people who had no cancer history orfamily cancer predispositions. Genomic DNA was extracted from the histologicallynormal formalin-fixed paraffin-embedded tissues in the distant margin to the gastriccancer and fresh blood of the controls. PCR-LDR and sequencing were used todetermine the genotypes and allele frenquency of rs11542705、 rs1883660of14-3-3σ geneResults:1.14-3-3σ protein positive particles were predominantly localized in the cytoplasm,brownish yellow granules, do not express or slight expression in normal gastricepithelial cells, the expression of14-3-3σ protein in gastric intestinal metaplasiamucosa was higher than in normal gastric mucosa.2. The expression of14-3-3σ protein in gastric cancer tissue were higher than innormal gastric mucosa.3. From the gastric mucosa layer to the invasiveness frontier, the expression of14-3-3σ protein showed downtrend, and from the invasiveness frontier to the metastasislymph nodes, The expression of14-3-3σ protein showed ascending tendency.4. The expression of14-3-3σ protein in early stage gastric mucosa cancer weresignificantly higher than that of progressive stage gastric mucosa cancer;5. The expression of14-3-3σ protein in High, poorly differentiated andundifferentiated adenocarcinoma is higher than mucinous adenocarcinoma, signet ringcell carcinoma.6. The expression of14-3-3σ protein in intestinal type and mixed type gastriccarcinoma was higher than diffused type gastric carcinoma.7. The expression of14-3-3σ protein in the center of the tumor and the metastasislymph nodes were negatively related with the survival time of patients after operation.8. There was no difference in distribution frequency of14-3-3σ rs11542705、rs1883660genotypes in the gastric carcinoma patients from controls. Conclusions:1. The expression of14-3-3σ protein is involved in the development, invasivenessand metastasis of gastric cancer, moreover,it is negatively related to the survival timeof patients after operation;2. There is no relationship between the polymorphism of14-3-3σ rs11542705、rs1883660and genetic predisposition of gastric cancer patients in Fujian province.