Expressions and mechanisms of ATPase family AAA domain-containing protein 2 and β-catenin in hepatocellular carcinoma / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the expressions of ATPase family AAA domain-containing protein 2 (ATAD2) and β-catenin,and to analyze their correlations with clinicopathological features and prognostic significance in patients with hepatocellular carcinoma (HCC).Methods The HCC tissues of 40 patients were tested by real-time PCR to study the expressions of ATAD2 and β-catenin.Real-time PCR and Western blot were performed to detect the proteins and mRNA levels of ATAD2,APC,β-catenin and wnt signaling pathway downstream.The HCC tissues of 80 patients and 20 peritumoral tissues were tested by immunohistochemistry (IHC).The cumulative survival-rate was analyzed by the Kaplan-Meier method,and univariate and multivariate were analyzed by the Cox proportional hazards model.Results ISHThe positive rates of ATAD2 and β-catenin were 65.0％ and 55.0％,respectively.These rates were significantly higher than those in the peritumoral tissues (30.0％ and 25.0％,respectively).The ATAD2 expression was related to tumor size (P ＜ 0.05),metastasis (P ＜ 0.05),serum AFP level (P ＜ 0.05) and TNM stag ing (P ＜ 0.05).The β-catenin expression was only significantly related to metastasis (P ＜ 0.05).Correlation analysis showed that the ATAD2 expression was positively related to the β-catenin expression (Pearson =0.578,P ＜ 0.01,R2 =0.3607,Spearman =0.495).This positive relationship was also found in the remaining 4 cell lines except the SK-hep1.Depleting ATAD2 up-regulated APC and down-regulated β-catenin protein and mRNA expression.Univariate and multivariate analyses showed that ATAD2 and β-catenin expressions,tumor size,metastasis,serum AFP,and TNM staging were poor prognostic factors for HCC,and ATAD2 and β-catenin expressions,metastasis,serum.AFP were independent prognostic factors.Patients whose ATAD2 and β-catenin were both positive had worse survival than those with only one positive expression or both negative expressions (P ＜ 0.05).Depleting ATAD2 down-regulated survivin,cyclinD1,c-myc,MMP7,Vimentin in wnt signaling pathway and EMT related proteins.Conclusions ATAD2 and β-catenin expressions were positively related in patients with HCC.Abnormal expressions between ATAD2 and β-catenin might participate in the wnt signaling pathway.