Significance Of Survivin And P27kip1 Protein In The Pathogenesis Of Hepatocellular Carcinoma

Backgrounds and ObjectivesSurvivin is a new member of inhibitor of apoptosis proteins(IAP) family. Current studies show that survivin has double regulating effects on apoptosis and cell cycle. It can inhibit the activity of the effective molecule caspase-3, which could block the apoptosis. Overexpression of Survivin in cancer cells may overcome this apoptosis-related cell cycle checkpoint and cause the increase of cell proliferation and decrease of apoptosis, unbalance of proliferation and apoptosis, and cause the occurrence and development of cancer.p27kipl is a member of the universal CKI family. Since the cloning of p27kipl gene in 1994, a host of other functions have been associated with the cell cycle protein in addition to its roles as a CKI; which can directly inhibit the enzymatic activity of cyclin-CDK complexes and arrest cells in G1, p27kip1 is a putative tumor suppressor gene, regulator of drug resistance in solid tumors, and promoter of apoptosis and has a role in cell differentiation. The level of p27kip1 protein expression decreases during tumor development in some malignant tumors. Many studies show that p27kipl gene mutant is rare and the expression level and activity are related to tumorigenesis and prognosis. Several studies have demonstrated that loss of p27kipl protein is a negative prognostic marker in breast, colon, lung, prostate cancer.Up to now, few studies have addressed the relationship between survivin or p27kipl protein expression and the cell apoptosis in HCC. In this work, we performed experiments to test the expressions of apoptosis inhibitor survivin and p27kipl protein, and the cell apoptosis in HCC. We also analyzed the relationship between survivin or p27kipl protein expression and the cell apoptosis in HCC, and evaluated their relationship with clinical pathologic features of patients with HCC.MethodsIn 40 specimens of HCC tissues, para-carcinoma tissues and normal hepatic tissues, the expression of survivin and p27kipl was detected by using immunhischemistry; TUNEL was used to detect the cell apoptosis in HCC tissue. Inspection standard a equal 0.05.Results1,The para-carcinoma tissues and normal hepatic tissues were completely negative for Survivin protein expression; The expression of Survivin protein in HCC tissues was higher than that in the para-carcinoma tissues and in normal hepatic tissues(P <0.05).2,The expression of p27kipl protein in HCC tissues was lower than that in the para-carcinoma tissues(P<0.05)and in normal hepatic tissues(P<0.05); It is not different for the expression of p27kipl proten in the para-carcinoma tissues and normal hepatic tissues(P>0.05).3,The expression of protein Survivin and p27kipl have no direct correlation with the sex, age, and AFP expressed by patients(P>0.05), but they have a close correlation with the intrahepatic metastasis, portal vein thrombosis(P<0.05). The expression of protein Survivin have correlations with Edmondson grading in patients(P<0.05). The expression of protein p27kipl have no correlations with Edmondson grading in patients(P>0.05).4,The average apoptosis level is (1.654±0.356)% in the 40 cases of HCC. AI in 34 cases of positive Survivin expression was (1.562±0.496)%, AI in 6 cases of negative Survivin expression was (4.082±0.830)%, the difference were significant(P<0.05); AI in 8 cases of positive p27kipl expression was (3.552±0.326)%, AI in 32 cases of negative p27kipl expression was (0.802±0.549)%, both the difference was significant (P<0.05). 5,The expression of Survivin protein in HCC tissues was negatively correlated with that of p27kipl protein in HCC (r=-0.758, P<0.05).Conclusions1,High level expression of Survivin protein in HCC tissues and low level expression of p27kipl protein in HCC tissues compared the para-carcinoma tissues and normal hepatic tissues, and the expression of Survivin protein in HCC tissues was negatively correlated with that of p27kipl protein in HCC, which suggested that it is closely related to the occurrence and development of HCC.2,The expression of protein Survivin and p27kipl have no direct correlation with the sex, age, and AFP expressed by patients, but they have a close correlation with the intrahepatic metastasis, portal vein thrombosis. The expression of protein Survivin have correlations with Edmondson grading in patients. The expression of protein p27kipl have no correlations with Edmondson grading in patients.3,The expressions of Survivin and p27kipl protein might influence the biological property by inhibiting cell apoptosis.