title: Overexpression of activated Cdc42-associated kinase1 (Ack1) predicts tumor recurrence and poor survival in human hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology and Institution of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pathology, Yuncheng Central Hospital of Shanxi Province, Yuncheng 044000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Hepatic Surgery, Liver Disease Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology and Institution of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Zang
authors.affiliation: Department of Pathology and Institution of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pathology and Institution of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China. Electronic address: Huangaimin2013@yeah.net.
authors.forename: Aimin
authors.initials: A
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C403262:TNK2 protein, human
keywords: Activated Cdc42-associated kinase1 (Ack1); Drug target; Hepatocellular carcinoma (HCC); Survival rate