RASSF1A，APC，WIF-1and RNF180Protein Expression And Their Clinical Significance In Hepatocellular Carcinoma

Objective: Hepatocellular carcinoma(HCC) is one of the commonmalignant tumors of the digestive system, its incidence and mortality in recentyears gradually increased, but its causes and pathogenesis is not yet clear.With the development of genetic testing technology and molecular biology,the role of tumor suppressor genes in tumor formation and developmentprocess was increasing emphasis. In this study, immunohistochemicaldetection was used for RASSF1A, APC, WIF-1and RNF180proteinexpression in HCC and cirrhosis tissues, and the corrections of the expressionof these tumor suppressor gene proteins with clinical features and pathologicalwere analyzed, and the prognostic significance for these gene proteins in HCCwas explored.Methods:1Patients：162HCC patients including135males and27females wereinvolved in this study.The diagnosis was confirmed by pathological specimencollected in the Fourth Hospital of Hebei Medical University between2002and2011.The patients,age was from24to79years old with the average age57.23±7.26. According to the TNM stages standard instituted by AGCC in2002, there were52cases in stageⅠ,66cases in stage Ⅱ,66cases in stageⅡa nd4cases in stage Ⅳ. Of268cases of specimens,86cases of HCC and30cases of corresponding paraneoplastic cirrhosis tissue were detected forRASSF1A, APC, WIF-1protein exprssion by immunohistochemical staining,76cases of HCC and76cases of corresponding paraneoplastic cirrhois for theRNF180detiection.All patients were followed up.2Immunohistochmical staining method: All specimens were embedded inparaffin.The deleation of RASSF1A, APC protein expressions were used byABC method,and WIF-1, RNF180protein expressions by SP method.The results of Immunohistochemisry were judged by semi-quantitative method.3Statistical analysis:All data were analyses using SPSS13.0software.Results:1Expression of RASSF1A, APC, WIF-1and RNF180in hepatocellularcarcinoma and in djacent non-cancerous liver tissues.RASSF1A positive expression observed in HCC showed a yellow orbrown staining. The positive rate of RASSF1A expression in HCC tissues was63.95%, while83.33%in adjacent non-cancerous liver tissues, the differencewas statistically significan（tP=0.048<0.05）. APC positive expression showeddark brown staining. The positive rate of APC expression in HCC tissues was67.44%, while86.67%in adjacent non-cancerous liver tissues, the differencewas statistically significant(P=0.014<0.05). WIF-1positive expression showeda yellow or brown cytolymp staining. The positive rate of WIF-1expression inHCC tissues was23.26%, while66.67%in adjacent non-cancerous livertissues, the difference was statistically significant(P=0.019<0.05). RNF180positive expression showed a yellow or brown cytolymp staining. The positiverate of RNF180expression in HCC tissues was63.15%, while86.84%inadjacent non-cancerous liver tissues, the difference was statisticallysignificant(P=0.006<0.05).2The relationship of RASSF1A, APC, WIF-1and RNF180expression withclinical pathological features.RASSF1A, APC and WIF-1protein expression were significantly lowerin patients than that with portal vein tumor thrombus (P<0.05). RASSF1A andAPC expression in pateints with stage Ⅰ to Ⅱwas significantly higher thanthat of stage Ⅲ to Ⅳ (P<0.05). RASSF1A expression in hepatocellularcarcinoma tissue envelope higher than in the non-enveloped HCC tissues (P=0.021<0.05). APC expression in HBsAg positive was significantly higherthan in HBsAg negative expression in HCC tissue (P=0.016<0.05), WIF-1expression in the tumor of sigle was significantly higher than that of tumormultiple (P=0.027<0.05). RASSF1A, APC and WIF-1expression in thepatients’ sex, age, AFP, Child-pugh grade and tumor size were unrelated. The RNF180protein expression had no relation with the patients’ age, gender,Child-pugh grade, tumor size, portal vein tumor thrombus, pathological grade,tumor number, clinical stage and HBsAg positive or negative, but RNF180protein positive expression in AFP≤200ug/L group was significantly higherthan AFP＞200ug/L (P=0.031<0.05).3The relationship between expression of RASSF1A, APC, WIF-1, RNF180and survival.The postoperative overall survival was no significantly different betweenthe patients with negatively RASSF1A expression and those with positiveexpression (mean survival duration:39.21±5.13vs33.56±4.26months. P=0.687>0.05).The postoperative overall survival was no significantly different betweenthe patients with negatively APC expression and those with positiveexpression (mean survival duration:40.69±5.36vs32.73±3.64months. P=0.217>0.05).The postoperative overall survival was no significantly different betweenthe patients with negatively WIF-1expression and those with positiveexpression (mean survival duration:36.58±5.31vs30.99±4.06months. P=0.917>0.05).The postoperative overall survival was significantly different between thepatients with negatively RNF180expression and those with positiveexpression (mean survival duration:16.42±6.39vs20.40±5.86months. P=0.002<0.05).Multivariate analysis showed that the factors of different AFP level, withor without portal vein tumor thrombosis, RNF180expression wereindependent prognosic significance.Conclusion:1Low expression of RASSF1A, APC, WIF-1and RNF180protein inhepatocellular carcinoma may be partly involved in the carcinogeneration ofHCC.2RASSF1A, APC and WIF-1protein expression were downregulation in the patients with portal vein tumor thrombus. It showed RASSF1A, APC andWIF-1protein expression may be promote the progress of hepatocellularcarcinoma. The low expression of RASSF1A, APC and WIF-1protein incancer tissues could be more likely to vascular invasion and metastasis.3Portal vein tumor thrombus and the RNF180protein expression levels are anindependent prognostic factor in patients with hepatocellular carcinoma.However, RASSF1A, APC and WIF-1protein expression can not be usedfor an independent prognostic independent factor in patients withhepatocellular carcinoma.