Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosisReport as inadecuate




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Journal of Translational Medicine

, 10:106

Cancer microenvironment

Abstract

BackgroundZinc-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.

MethodsQuantitative 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.

ResultsAZGP1 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.

ConclusionAZGP1 was downregulated in HCC and could be served as a promising prognostic marker for HCC patients.

KeywordsAZGP1 Hepatocellular carcinoma Prognosis Recurrence Metastasis AbbreviationsAZGP1Zinc-alpha2-glycoprotein

HCCHepatocellular carcinoma

qRT-PCRQuantitative real-time polymerase chain reaction

IHCImmunohistochemistry

AFPAlpha-fetoprotein

HBVHepatitis B virus

HCVHepatitis C virus

HBsAgHepatitis B surface antigen

MHC IMajor histocompatibility complex class I

ICGR15The 15-min retention rate for indocyanine green

TNMTumor-lymph node-metastasis

TMATissue microarray

OSOverall survival

DFSDisease-free survival.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-106 contains supplementary material, which is available to authorized users.

Yan Huang, Lin-Zi Li contributed equally to this work.

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Author: Yan Huang - Lin-Zi Li - Chris Zhi-Yi Zhang - Chun Yi - Li-Li Liu - Xuan Zhou - Guo-Bing Xie - Mu-Yan Cai - Yan Li - Jing

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