Expression Of CREB1 And PAK4 In Different Gastric Lesions And Their Relationship To Clinicopathologic Significance Of Gastric Adenocarcinoma

Objective:To investigate the expression of CREB1 and PAK4 in different gastric lesions,and to explore the relationship between the expression of CREB1,PAK4 and the tumor occurrence,prognosis,clinicopathological characters of gastric adenocarcinoma,and also the correlation between the expression of CREB1and PAK4.Methods:The expression of CREB1 and PAK4 was detected immunohistochemistrically in 92 cases of advanced gastric adenocarcinoma and corresponding adjacent non-neoplastic tissue,16 cases of gastric low-grade intraepithelial neoplasia and 15 cases of gastric high-grade intraepithelial neoplasia tissue.The relationship between the expression of CREB1,PAK4 and the occurrence of gastric adenocarcinoma,clinicopathological characters,prognosis of advanced gastric adenocarcinoma was analyzed by statistical methods.Results:The expression of CREB1 in low-grade intraepithelial neoplasia tissue(?2=6.361,P=0.030),high-grade intraepithelial neoplasia tissue(?2=15.210,P=0.001)and advanced gastric adenocarcinoma tissue(?2=32.305,P<0.001)was significantly higher than that in corresponding adjacent non-neoplastic tissue.However,there was no obvious difference in the level of CREB1 expression between low-grade intraepithelial neoplasia tissue and high-grade intraepithelial neoplasia tissue,which was also the same between low-grade intraepithelial neoplasia tissue and advanced gastric adenocarcinoma tissue,between high-grade intraepithelial neoplasia tissue and advanced gastric adenocarcinoma tissue(P>0.05,respectively).The expression of PAK4 in advanced gastric adenocarcinoma tissue was both significantly higher than that in corresponding adjacent non-neoplastic tissue(?~2=27.173,P<0.001)and low-grade intraepithelial neoplasia tissue(?~2=5.171,P=0.023).However,there was no obvious difference in the level of PAK4 expression between corresponding adjacent non-neoplastic tissue and low-grade intraepithelial neoplasia tissue,which was also the same between corresponding adjacent non-neoplastic tissue and high-grade intraepithelial neoplasia tissue,between low-grade intraepithelial neoplasia tissue and high-grade intraepithelial neoplasia tissue,between high-grade intraepithelial neoplasia tissue and advanced gastric adenocarcinoma tissue(P>0.05,respectively).CREB1 expression in advanced gastric adenocarcinoma was related to TNM grade(?~2=4.168,P=0.041),depth of invasion(?~2=4.378,P=0.036)and vascular invasion(?~2=8.802,P=0.003),but not to gender,age,differentiation,size of the tumor,and Lymph node metastasis(P>0.05,respectively).PAK4 expression in advanced gastric adenocarcinoma was related to TNM grade(?~2=4.985,P=0.026)and lymph node metastasis(?~2=6.179,P=0.013),but not to gender,age,size of the tumor,the depth of invasion and vascular invasion(P>0.05,respectively).Patient with high expression of CREB1 and PAK4 had shorter overall(?~2=6.790,P=0.009),(?~2=9.155,P=0.002)and disease-free(?~2=6.418,P=0.011),(?~2=9.313,P=0.002)survival time than patient with low expression in advanced gastric adenocarcinoma.Cox multivariate analysis showed that the high expression of both CREB1 and PAK4 were independent risk factors affecting prognosis in advanced gastric adenocarcinoma patient.The expression of CREB1 and PAK4 in advanced gastric adenocarcinoma was obvious positively correlated(r=0.381,P<0.001).Conclusion:CREB1 and PAK4 may be involved in the tumorigenesis and progress of gastric adenocarcinoma,and may have a synergistic effect;High expression of CREB1 and PAK4 is an independent risk factor affecting prognosis in advanced gastric adenocarcinoma patient,and suggests that it may be an important prognostic indicator of advanced gastric adenocarcinoma.