Expression And Clinical Significance Of Livin And Caspase-3 In Cholangiocarcinoma

ObjectiveCholangiocarcinoma is one of the most common malignant tumors in bile duct.Recently, the morbidity of Cholangiocarcinoma has been in increasing tendency from epidemiological survey. Cholangiocarcinoma is a kind of carcinoma with poor prognosis because of its lately symptom emergence, harld early diagnosis and low radical cure rate. Terefore, investigation of the mechanism of cholangiocarcinoma is important to elevate the diagnosis and treatment of the cholangiocarcinoma.Modern molecular biology studies have showen that the formation and development of malignant tumors are not only associated with abnormal proliferation and differentiation, but also involved in inhibition of apoptosis which was one of the important mechanisms in the forming of tumors.So,apoptosis and tumor became a new focus in molecular biological researches. Livin is a novel inhibitor of apoptosis protein with oncogene potentiality recently discovered. Livin is presented in several cancer cell lines, so it has close relation with the occurrence of tumors. Livin served as a new target for apoptosis-inducing therapy of cancer.Caspase family is a class of amino acid sequence, spatial structure and substrate specificity are similar specificity of aspartic acid-cysteine protease. The occurrence of apoptosis is a complex, mediated by the Caspase family members of the protease cascade process, but the district is located downstream effector Caspase-3 activation was considered to be the only way cascade. Livin mainly through its BIR District and cysteine aspartate-specific proteases (Caspases) combination of direct inhibition of cysteine protease caspases, in particular, inhibit Caspase-3/-7 and Caspase-9 activity, to resistance fault-related apoptosis receptor and mitochondrial apoptosis pathway, while the realization of the inhibition of apoptosis.This experiment is to study the expression of Livin and Caspase-3 in cholangiocarcinoma, and explore Livin and Caspase-3 expression in the relationship with the biological behavior of cholangiocarcinoma; and cholangiocarcinoma in correlation between the two preliminary studies, further explore the Livin and Caspase-3 occurrence of cholangiocarcinoma, the development impact, revealing the pathogenesis of cholangiocarcinoma; for the diagnosis and treatment of cholangiocarcinoma to find a possible new target.Methods56 cholangiocarcinoma specimens confirmed by the postoperative pathologic diagnosis were selected from the Surgery of the First Affiliated Hospital of China Medical University General from Jan of 2002 to Dec of 2008. Adjacent bile duct tissue samples from 29 cases of radical resection of the specimen without cancer confirmed by pathology. We detected the expression of Livin and Caspase-3 in the Cholangiocarcinoma tissue by immunologic histochemistry methods. Statistic analysis was completed with SPSS 13.0. All data were tested by x2-test or Spearman rank correlation test(P<0.05 was considered statistical significance). To investigate the correlation of the expression of Livin and Caspase-3 with clinical pathological characteristics in Cholangiocarcinoma and the correlation between Livin and Caspase-3.Results1,The expression of Livin protein in cholangiocarcinoma and bile duct cancer adjacent tissuesThe Livin expression rate in cholangiocarcinoma was 58.93% (33/56), but there was no expression of Livin in bile duct cancer adjacent tissues. The difference was significant (x2=26.094, P＜0.05). (Table 1). The tissues of cholangiocarcinoma are divided into male and female groups, Livin-positive rates were 52.94%(18/34) and 68.18%(15/22), respectively. There was no statistical significance between them (χ2=1.259, P>0.05). The expression rate of Livin in high, middle and low histological differentiation groups were37.93%(11/29),76.92%(10/13),85.71%(12/14), respectively. There was significant association between them (χ2=10.793, P<0.05). Livin positive rate was 61.29%(19/31) in patients with lymph node metastasis and 56.00%(14/25) in those without lymph node metastasis.There was no statistical significance between them (χ2=0.157, P>0.05). In cholangiocarcinoma, Livin total positive rate was 52.38%(11/21) in stagesⅠandⅡ, and 62.86%(22/35)in stage III andⅣ, respectively. Also, there was no statistical significance between them (χ2=0.585, P>0.05) (Table 4).2,The expression of Caspase-3 protein in cholangiocarcinoma and bile duct cancer adjacent tissuesThe Caspase-3 expression rate in cholangiocarcinoma was 39.29%(22/56), but the expression of Caspase-3 in bile duct cancer adjacent tissues was 88.89%(24/27). The difference was significant (χ2=14.01,P＜0.05) (Table 2). The tissues of cholangiocarcinoma are divided into male and female groups, Caspase-3-positive rates were 41.18%(14/34) and 36.36%(8/22), respectively. There was no statistical significance between them (χ2=0.127,P>0.05). The expression rate of Caspase-3 in high, middle and low histological differentiation groups were 58.62%(17/29), 30.77%(4/13),7.14%(1/14), respectively. There was significant association between them (χ2=10.808,P＜0.05). Caspase-3 positive rate was 41.94%(13/31)in patients with lymph node metastasis and 36.00%(9/25) in those without lymph node metastasis. There was no statistical significance between them (χ2=0.201, P>0.05). In cholangiocarcinoma, Caspase-3 total positive rate was 39.00%(8/21) in stagesⅠandⅡ, and 40.00%(14/35) in stageⅢandⅣ,respectively. Also,there was no statistical significance between them (χ2=0.020, P>0.05) (Table 5).3,The correlation between the expressions of Livin and Caspase-3 in cholangiocarcinoma The Spearman rank correlation analysis method was used to analyze the correlation of Livin and Caspase-3. It showed that the expression of Livin was negative related to that of Caspase-3 in cholangiocarcinoma (r=-0.295, P=0.028<0.05) (Table 3).Conclusion1. The positive expression rates of Livin protein were higher in cholangiocarcinoma than in bile duct cancer adjacent tissues. It suggested that Livin protein expression was related with the development and progression of cholangiocarcinoma.2. The expression rates of Caspase-3 protein decreased from bile duct cancer adjacent tissues to cholangiocarcinoma. It suggested that the decrease of Caspase-3 protein expression correlated with the development and progression of cholangiocarcinoma.3. Both Livin and caspase-3 protein expression in cholangiocarcinoma had no significant correlation with patient's sex, lymph nodes metastasis or not and TNM stages, but had significant correlation with patient's cell differentiation level.4. In cholangiocarcinoma, Livin was negative related to that of Caspase-3. Livin protein activation and Caspase-3 inactivation involved in the pathogenesis of cholangiocarcinoma.