Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosis
Menée sur 246 patients atteints d'un carcinome hépatocellulaire, cette étude évalue l'association entre l'expression de la glycoprotéine AZGP1 et le pronostice de la maladie
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).CONCLUSION:AZGP1 was downregulated in HCC and could be served as a promising prognostic marker for HCC patients.
Journal of Translational Medicine , article en libre accès, 2011