Expression And Clinical Significance Of Skp2 And P27 In Human Hepatocellelar Carcinoma

Objective: The hepatocellular carcinoma (HCC) is one of the most common malignant tumors in our country, which still is the second cause of death in cancers although with operation or intervention treatment. To identify the mechanisms of development and to search effective approaches to treat HCC remain a challenge to modern medical science. The investigation in gene level to tumor receives reconstruction increasingly. Recently, it has been reported that tumor is a disease because of multiple gene changing which lead to cell cycle's disorder and loss of control in cell growth. P27 as one of cyclin-dependent kinase inhibitors (CKI) belong to anti-oncogene. P27 can stop cell growth at G1 by inhibiting cyclin-dependent kinase (CDK) and inhibiting cyclin-CDK's activity. S-phase kinase-associated protein 2 (Skp2) is discovered recently as one of F-box protein family. Skp2 can discriminate cyclin-CDK to make p27 phosphorylation, then disintegrate p27 by ubiquitin-proteasome pathway, by which Skp2 participates the control to cell cycle. By testing the expressions of Skp2 and p27 in primary HCC tissues, tumor-surrounding tissues and normal liver tissues, we want to determine the relationship between the two factors. The aim of this experiment was to document the relationship in the development and clinical significance of HCC tissues with Skp2 and p27.Methods: Forty-six tumor tissue samples and thirty tumor-surrounding tissue samples were obtained from primary HCC patients undergoing surgical resection. Twenty normal liver tissue samples were taken from previously patients with benign tumor. S-P method of Immunohistochemistry was used to detect the expression of Skp2 and p27. Statistical analysis was used to determine the relationship between their expression and clinical marker.Results: 1 Skp2 protein stain In HCC: Skp2-positive stain was observed in fifteen of 46 tumor tissue (32.6%). In contrast, Skp2-positive stain was only in 2 of 30 tumor-surrounding tissue (6.67%). Only one of 20 (5%) Skp2-positive stain in normal liver tissue was observed. Statistical analysis revealed that Skp2-positive stain rate was higher in tumor tissue than that in tumor-surrounding tissue and in normal liver tissue (P<0.05).2 Positive rate of Skp2 protein in HCC became higher when tumor differentiation degree went poorer. The positive rate of Skp2 protein in well differentiated carcinoma was 10%, whereas it was 50% in poorly differentiated carcinoma, which difference was statistically significant (P=0.004).3 The expression of Skp2 had significant correlation with intrahepatic or lymphatic metastasis and portal vein or biliary duct tumor thrombosis, which difference was significant in statistics (P<0.05), whereas no relationships of it with age, sex, tumor size, liver cirrhosis and AFP were observed (P>0.05).4 P27 protein stain in HCC: p27-positive stain was observed in twenty of 46 tumor tissue (43.5%). In contrast, p27-positive stain was observed in 25 of 30 tumor-surrounding tissue (83.3%). Seventeen of 20 (85%) Skp2-positive stain in normal liver tissue was observed. Statistical analysis revealed that Skp2-positive stain rate was lower in tumor tissue than that in tumor-surrounding tissue and in normal liver tissue (P<0.05).5 Positive rate of p27 protein in HCC became lower when tumor differentiation degree went poorer. The positive rate of p27 protein in well differentiated carcinoma was 70%, whereas it was 23.1% in poorly differentiated carcinoma, which difference was statistically significant (P=0.001).6 The expression of p27 had significant correlation with intrahepatic or lymphatic metastasis, portal vein or biliary duct tumor thrombosis and tumor size which difference was significant in statistics (P<0.05), whereas no relationships of it with age, sex, liver cirrhosis and AFP were observed (P>0.05).7 Spearman's rank correlation test showed that Skp2 expression in HCC had negative correlation with p27 expression. Correlation coefficient: r=-0.329, P=0.025.Conclusion: 1 Skp2 expressed low in normal liver tissue and tumor-surrounding tissue, high in HCC. Skp2 became gradually higher in expression when the degree of tumor differentiation became poorer. It indicated that Skp2-positive expression was associated with the occurrence and development of HCC.2 P27 expressed high in normal liver tissue and tumor-surrounding tissue, low in HCC. P27 became gradually lower in expression when the degree of tumor differentiation became poorer. It indicated that the loss or devitalization of p27 was associated with HCC.3 The expressions of Skp2 had remarkable correlations with intrahepatic or lymphatic metastasis and portal vein or biliary duct tumor thrombosis (P<0.05), whereas no relationships of it with age, sex, tumor size, liver cirrhosis and AFP were observed (P>0.05). The expressions of p27 had remarkable correlations with intrahepatic or lymphatic metastasis, portal vein or biliary duct tumor thrombosis and tumor size (P<0.05), whereas no relationships of it with age, sex, liver cirrhosis and AFP were observed (P>0.05). It indicated that Skp2 and p27 closely related to malignant biological behaviour of HCC.4 Spearman's rank correlation test showed that Skp2 expression in cervical carcinoma had negative correlation with p27 expression, which indicated that the degradation of p27 protein is possible to complete by ubiquitin-proteasome pathway. Over expression of Skp2 along with low expression of p27 may indicate a tumor with higher invasive tendency and poor prognosis.5 Skp2 and p27 can be used as the independent indicators for the prognosis and provide a new target to the treatment of HCC.