Expressions and mechanisms of ATPase family AAA domain-containing protein 2 and β-catenin in hepatocellular carcinoma

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 ISH: The 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 staging (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. Key words: Hepatocellular carcinoma; ATPase family AAA domain-containing protein2 (ATAD2); β-catenin; Wnt signaling pathway