Clinicopathologic Significance Of Sirt1 And P300/cbp Expression In Gastric Cardia Carcinoma

Objective: To investigate the expression of SIRT1 and p300/CBP in gastric cardia carcinoma, analysis their clinicopathologic significance and correlationship with relative genes'expression level, in order to discuss the formation and progression mechanisms of gastric cardia carcinoma.Methods: The tissue microarray (TMA) technique and immunohistochemistry stain were used to detect the expression of SIRT1, p300/CBP, p53, Ki-67, E-cadherin and MLH1 in 176 gastric cardia carcinoma tissues and 32 normal gastric cardiac region tissues, and analysis the clinicopathologic significance and prognosis correlation of SIRT1 and p300/CBP expression and their correlationship with p53, Ki-67, E-cadherin and MLH1.Results: In the 176 gastric cardia carcinoma, expression of SIRT1 was significantly higher than that of in the 32 normal gastric cardia region tissues (P<0.01), and was associated with the lymphatic metastasis (P<0.05), TNM stage (P<0.05), Ki-67 level (P<0.05), E-cadherin (P<0.05) and MLH1 (P<0.01) expression; the difference between the expression of p300/CBP in the gastric cardia carcinoma and that of in the normal gastric cardia region tissues were not of statistical significance (P>0.05), and the p300/CBP expression in the gastric cardia carcinoma was associated with the Ki-67 level (P<0.001), p53 (P<0.05), E-cadherin (P<0.001) and MLH1 (P<0.001) expression; in the 90 cases with complete follow up information, the three-year survival rate and mean survival time of patients with positive SIRT1 expression were significantly lower than that of patients with negative SIRT1 expression (P<0.05), the three-year survival rate and mean survival time of patients with higher expression of E-cadherin (P≤0.001) and MLH1 (P<0.05) were significantly higher than that of with lower expression of the two markers; COX regression analysis showed that the lymphatic metastatic condition was an independent factor that affect the prognosis of gastric cardia carcinoma (P<0.001), the expression of SIRT1 and p300/CBP were not significantly associated with the prognosis of gastric cardia carcinoma (P>0.05).Conclusions: There existed over-expression of SIRT1 in gastric cardia carcinoma, and SIRT1 expression was correlated with lymphatic metastasis, TNM stage, proliferative status and survival time; the expression of SIRT1 was correlated with the E-cadherin and MLH1 level, SIRT1 might be a promoter that activates the growth and progression of gastric cardia carcinoma; the protein level of p300/CBP in gastric cardia carcinoma was associated with the cellular proliferative status, and was correlated with the expression of p53, E-cadherin and MLH1; p300/CBP might be a tumor-suppressor gene, however in the aspect of cell proliferation, p300/CBP might be a promoter rather than a suppressor; SIRT1 and p300/CBP might play inverse roles in regulating the expression of E-cadherin and MLH1, thus affected the clinicopathologic features of gastric cardia carcinoma such as biological behaviors and survival time; SIRT1 and p300/CBP combined with E-cadherin and MLH1 might be biological parameters to evaluate the malignant degree of gastric cardia carcinoma and forecast the survival condition of gastric cardia carcinoma; the lymphatic metastasic condition could be served as an independent factor that effect the prognosis of gastric cardia carcinoma, to improve the accuracy of the lymphatic metastasic diagnosis might be helpful to predict the prognosis of gastric cardia carcinoma patients.