title: Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosis.
abstract: BACKGROUND
  Zinc-alpha2-glycoprotein (AZGP1, ZAG) was recently demonstrated to be an important factor in tumor carcinogenesis. However, AZGP1 expression in hepatocellular carcinoma (HCC) and its significance remain largely unknown.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine mRNA level of AZGP1 in 20 paired fresh HCC tissues. Clinical and pathological data of 246 HCC patients were collected. Tissue-microarray-based immunohistochemistry (IHC) was performed to examine AZGP1 expression in HCC samples. Relationship between AZGP1 expression and clinicopathological features was analyzed by Chi-square test, Kaplan-Meier analysis and Cox proportional hazards regression model.
  
  
  RESULTS
  AZGP1 expression was significantly lower in 80.0% (16/20) of tumorous tissues than that in the corresponding adjacent nontumorous liver tissues (P < 0.001). Consistently, IHC data revealed that decreased expression of AZGP1 was present in 80.1% (197/246) of HCC patient tissues (P < 0.001). Furthermore, AZGP1 expression in HCC significantly associated with several clinicopathological parameters, including serum AFP level (P = 0.013), liver cirrhosis (P = 0.002) and tumor differentiation (P = 0.025). Moreover, HCC patients with high AZGP1 expression survived longer, with better overall survival (P = 0.006) and disease-free survival (P = 0.025). In addition, low AZGP1 expression associated with worse relapse-free survival (P = 0.046) and distant metastatic progression-free survival (P = 0.036).
  
  
  CONCLUSIONS
  AZGP1 was downregulated in HCC and could be served as a promising prognostic marker for HCC patients.
authors.affiliation: Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Lin-Zi
authors.initials: LZ
authors.lastname: Li
authors.forename: Chris Zhi-Yi
authors.initials: CZ
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Yi
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Guo-Bing
authors.initials: GB
authors.lastname: Xie
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Yun
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D029589:Seminal Plasma Proteins / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein