Expression Of XIAP, Survivin, Caspase-3 And Their Prognostic Significance In Pancreatic Carcinoma

Objective: IAPs is a group of structurally related proteins which can inhibit apoptosis. XIAP and Survivin are the most important members in the family, which can inhibit caspase-dependent or caspase-non-dependent apoptosis pathway directly or indirectly. Caspase-3 is the main effect factor in apoptosis. There are many reports about XIAP and Survivin expression in pancreatic carcinoma, while few studies about Caspase-3 expression and relationship of the three proteins in pancreatic carcinoma. Our study explored the expression of XIAP, Survivin and Caspase-3 in pancreatic carcinoma tissues and normal pancreatic tissues, to evaluate the correlation of XIAP,Survivin and Caspase-3 expression with the clinical pathological features and the survival of patients,and to approach the roles of these proteins in the development and prognosis of pancreatic carcinoma.Methods:1 54 pancreatic carcinoma samples were surgically removed between 2003 and 2009 from the patients including 34 males and 20 females with average age of 60.91 in the Forth Hospital of Hebei Medical University. We also collected 14 normal pancreatic tissue samples as comparison. According to the TNM stages standard instituted by AGCC in 2002, 18 samples in stageⅠ, 19 in stageⅡ, 4 in stageⅢand 13 in stageⅣwere used.All cases were followed up. Tissue specimens were fixed in 10% buffered formalin and embedded in paraffin and performed on 4-μm sections for 5 pieces. After HE stained, the slides were grades by two pathological physicians. Meanwhile, we determined the pathological grade and vascular invasion or lymph node metastasis.2 Expression of XIAP, Survivin and Caspase-3 were examined by immunohistochemistry in all pancreatic tissues. A semiquantitative scoring system was used to assess XIAP, Survivin and Caspase-3 reactively. Specific steps were in accordance with kit instructions. The results of immunohistochemistry were refered to common standard. 3 All statistical analyses were performed using SPSS 13.0 software.Results:1 Expression of XIAP, Survivin, Caspase-3 in pancreatic carcinoma tissues and in normal pancreatic tissuesXIAP positive expression observed in pancreatic cancer showed a yellow or brown cytolymp staining. The positive rate of XIAP expression in pancreatic carcinoma tissues was 88.9%, while50.0% in normal pancreatic tissues, the difference was statistically significant(χ2=10.87, P=0.001<0.05). Survivin positive expression showed a dark brown or granular cytoplasm staining. The positive rate of Survivin expression in pancreatic carcinoma tissues was 85.2%, while 35.7% in normal pancreatic tissues, the difference was statistically significant(χ2 =14.51, P=0.000<0.05). Caspase-3 positive expression showed a yellow or brown cytolymp staining. The positive rate of Caspase-3 expression in pancreatic carcinoma tissues was 87.0%, while 35.7% in normal pancreatic tissues, the difference was statistically significant(χ2=16.28,P=0.000<0.05).2 The relationship of XIAP, Survivin and Caspase-3 expression with clinical pathological features and TNM stagesThe expression of XIAP,Survivin and Caspase-3 were not related to sex, age, location,abdominal pain, jaundice and TNM stages. The XIAP and Survivin expression had correlation with vessel invasion or lymph node metastasis, but the differences in the expression of Caspase-3 was not significant. Survivin expression had correlation with tumor size.3 The relationship between tumor differentiation and XIAP, Survivin and Caspase-3 expressionXIAP and Survivin expression were negatively correlated with differentiation grades(r=-0.331, P=0.014< 0. 05; r=-0.353,P=0.009< 0. 05). With the lower degree of differentiation, XIAP and Survivin expression were gradually increased. Caspase-3 expression was positively correlated with differentiation grades(r=0.272, P=0.047< 0. 05). With the lower degree of differentiation, XIAP and Survivin expression were gradually decreased.4 The correlation of XIAP, Survivin and Caspase-3 expression in pancreatic carcinomaThe XIAP expression had positive correlation with Survivin expression; The XIAP expression had negative correlation with Caspase-3 expression; The Survivin expression had negative correlation with Caspase-3 expression.5 The relationship between expression of XIAP,Survivin,Caspase-3 and survivalThe survival rate was significantly different between the patients(mean survival time:16.37months) with negatively and weakly positive XIAP expression and those (mean survival time: 11.45months) with moderately and strongly positive expression( P = 0.041<0.05), so was significantly different between the patients (mean survival time: 7.76monthsVS16.11months)with different Caspase-3 expression. There was no significant difference in survival rate between patients with negatively and weakly positive Survivin expression and those with moderately and strongly positive expression.Multivariate analysis showed that the differentiation degree, TNM stage, Caspase-3 expression, lymph node metastasis and vessel invasion were independent prognosic factors.Conclusion:1 The level of XIAP and Survivin expression in pancreatic carcinoma tissues was higher than that in the normal pancreatic tissues; the XIAP and Survivin expression were negatively correlated with histological differentiation; the expression of XIAP and Survivin in pancreatic carcinoma tissues with vascular invasion or lymph node metastasis was significantly higher than that with no vascular invasion or lymph node metastasis. XIAP and Survivin participate in the development of pancreatic cancer, the high expression of XIAP and Survivin suggest pancreatic carcinoma has a more malignant biological behavior and a higher chance of vascular invasion or lymph node metastasis.2 Caspase-3 was high expressed in pancreatic cancer, and was positively correlated with histological differentiation. Caspase-3 takes an important role in the development of pancreatic cancer, and high expression suggests a well biological behavior.3 The correlation of XIAP,Survivin and Caspase-3 expression in pancreatic carcinoma furtherly illustrated that XIAP and Survivin inhibited the apoptosis of tumor cell by inhibiting the expression of Caspase-3.4 The survival of patients with low expression of XIAP was significantly higher than that of patients with high expression, Caspase-3 was just the opposite.That help us estimate the prognosis of pancreatic carcinoma. The expression level of Caspase-3 could be used as an valuable index for predicting the prognosis.