title: Prognostic significance of cytoskeleton-associated membrane protein 4 and its palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma.
abstract: BACKGROUND
  The functions of cytoskeleton-associated membrane protein 4 (CKAP4), one kind of type II transmembrane protein, are associated with the palmitoyl acyltransferase DHHC2. The objective of the current study was to investigate CKAP4/DHHC2 expression and its prognostic significance in patients with hepatocellular carcinoma (HCC).
  
  
  METHODS
  Two independent cohorts of 416 patients with HCC were enrolled. All the patients included had defined clinicopathologic and follow-up data. Using real-time polymerase chain reaction and immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The association between CKAP4/DHHC2 expression and HCC-specific disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses.
  
  
  RESULTS
  The data documented that CKAP4 expression was much higher in HCC tumor tissues compared with adjacent normal tissues and its expression was significantly correlated with tumor size, intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients with high CKAP4 expression appeared to have a favorable overall survival and a longer disease-free survival compared with those with low expression. DHHC2 expression was also examined in tissue microarray analysis by immunohistochemistry and the results demonstrated that 87.6% of the cases had low expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2 expression predicted favorable overall survival and disease-free survival rates in both the training cohort and validation set. Furthermore, the combination of CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis prediction than either one alone.
  
  
  CONCLUSIONS
  To the best of our knowledge, the current study is the first to demonstrate that the expression of CKAP4 and its palmitoyl acyltransferase DHHC2 correlates with disease progression and metastasis in patients with HCC and may provide prognostic and therapeutic value.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai, China; National Center for Liver Cancer, Shanghai, China; Department of Liver Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Li
authors.forename: Gu-Sheng
authors.initials: GS
authors.lastname: Tang
authors.forename: Dong-Xun
authors.initials: DX
authors.lastname: Zhou
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Pan
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Ding
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Jiang
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Hu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Dong
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000217:Acyltransferases / Q000032:analysis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D002681:China; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D019308:Palmitic Acid / Q000378:metabolism; D011169:Portal Vein / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D019308:Palmitic Acid; D000217:Acyltransferases; C532036:ZDHHC2 protein, human
keywords: DHHC2; cytoskeleton-associated membrane protein 4; hepatocellular carcinoma; prognosis