Overexpression of activated Cdc42-associated kinase1 (Ack1) predicts tumor recurrence and poor survival in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers in China. Recent research suggested that activated Cdc42-associated kinase 1 (Ack1) played an important role in facilitating tumorigenesis, tumor invasion and metastasis. However, the role of Ack1 in HCC is not clear. Herein, the expression level of Ack1 mRNA in 30 fresh HCC specimens (carcinoma, peri-carcinoma and distal-carcinoma tissues) was detected by reverse transcription-polymerase chain reaction (RT-PCR), while the expression of Ack1 protein in 18 fresh HCC specimens (carcinoma, peri-carcinoma and distal-carcinoma tissues) was analyzed by Western blotting. Immunohistochemical (IHC) staining was also employed to assess both the expression level and distribution of Ack1 protein in HCC tissues collected from 173 lesions, so as to study the correlations between Ack1 protein expression and other HCC-related clinicopathologic parameters. The results showed that both Ack1 mRNA and protein were significantly over-expressed in HCC tissues than that of either peri-carcinoma or distal-carcinoma tissues (P < 0.001, P = 0.012, respectively), while there was no significant difference between peri-carcinoma and distal-carcinoma tissues. Furthermore, the results of IHC indicated that the rates of Ack1 expressions in the patients with capsular invasion, hepatic vessel involvement and recurrence were higher than without above three conditions (P = 0.037, P = 0.036, P = 0.019, respectively), whereas the patients with overexpression of Ack1 protein had low survival rate (P = 0.007). Ack1 expression, tumor size and recurrence were independently related to survival (P = 0.014, P = 0.018, P < 0.001, respectively). Thus, the level of Ack1 is associated with tumor invasion potential, and the expression of Ack1 plays an important role as predictor of recurrence and poor outcome in HCC patients.