Significance Of Expression And SNPs Of Axl In Occurrence And Development Of Gastric Carcinoma

Background:Receptor tyrosine kinases(RTKs) is the largest group of enzyme-linkedreceptors in the human body and plays a variety of physiological andpathological functions.(Anexelekto) Axl is one of the genes encoding receptortyrosine kinase, and is associated with occurrence, development andprognosis of various tumors.Objective:1.To explore the significance of Axl gene expression with clinicopathologicalfeatures in gastric cancer,2.To investigate the role of SNPs of Axl gene rs8101017, rs73045231andrs117588892in the genesis and progression of gastric cancer.Methods:1.Tissue microarray was made:333cases after surgical operation in the FirstAffiliated Hospital of Fujian Medical University from January2001to December2009have the complete following-up data. All the cases were chosen from fivedifferent sites of the normal formalin-fixed paraffin-embedded tissues: thenormal gastric mucosa tissue, gastric cancer tissue of mucous layer, the centerof the tumor, the invasiveness frontier and the metastasis lymph nodes.39cases were chosen another site of intestinal metaplasia mucosa. Three piecesof tissues were drawn at each site then tissue microarray was made.2.The expression of Axl was detected by immunohistochemistry.3.Five SNPs of Axl gene were explored by PCR-LDR method:483cases ofgastric carcinoma after surgical operation in the First Affiliated HospitalofFujian Medical University from January2001to December2009was collected,620healthy controls were recruited from routine check-up peoplewho had no cancer history or family cancer predispositions. Genomic DNA wasextracted from the histologically routine formalin-fixed paraffin-embeddedtissues in the distant margin to the gastric cancer and fresh blood of thecontrols. PCR-LDR and sequencing were used to determine the genotypesand allele frequency of rs8101017, rs73045231and rs117588892of Axl gene.Results:1.Axl protein positive particles were predominantly localized in the cytoplasm,brownish yellow granules, do not express or slight expression in normal gastricepithelial cells, the expression of Axl protein in gastric intestinal metaplasiamucosa was higher than in normal gastric mucosa.2.The expression of Axl protein in gastric cancer tissue of mucous layer, thecenter of the tumor, the invasiveness frontier and the metastasis lymph nodeswere all higher than in normal gastric mucosa.3.From the gastric mucosa layer to the invasiveness frontier, the expression ofAxl protein showed downtrend, and from the invasiveness frontier to themetastasis lymph nodes. The expression of Axl protein showed ascendingtendency.4.The expression of Axl protein in gastric cancer tissue at the metastasislymph nodes was higher than mucous layer, the center of the tumor and theinvasiveness frontier.5.The expression of Axl protein in intestinal type gastric carcinoma was higherthan diffused type gastric carcinoma.6.The expression of Axl protein in the center of the gastric carcinoma werenegatively related with the survival time of patients after operation.7.There was no difference in distribution frequency of Axl rs8101017,rs73045231and rs117588892genotypes in the gastric carcinoma patientsfrom controls.8.The genotypes of Axl rs8101017, rs73045231and rs117588892were negatively related with the survival time of patients after operation.Conclusions:1.The expression of Axl protein is involved in the development, invasivenessand metastasis of gastric cancer, moreover, it is negatively related to thesurvival time of patients after operation;2.There is no relationship between the polymorphism of Axl rs8101017,rs73045231and rs117588892and genetic predisposition of gastric cancerpatients in Fujian province.