High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma.

Abstract:

BACKGROUND/AIMS:To investigate the prognostic values of putative hepatic stem/progenitor cell (HSC/HPC) biomarkers in patients with hepatocellular carcinoma (HCC). METHODS:Fourteen biomarkers related to HSCs/HPCs or tumour angiogenesis were assessed by qRT-PCR and then validated by tissue microarrays (TMAs) in three independent cohorts of patients with HCC undergoing curative resection (n=67, 314 and 73). RESULTS:Most of the biomarkers were found to be overexpressed in patients with recurrent HCC by quantitative reverse transcription-PCR (qRT-PCR). The HSC/HPC biomarkers cytokeratin 19, ATP-binding cassette subfamily G member 2 (ABCG2), CD133, Nestin and CD44, and the markers of angiogenesis microvessel density (MVD, determined by CD34 immunostaining), vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were confirmed as significant predictors for overall survival (OS) and/or relapse-free survival (RFS) in TMA analysis. As compared with the low HSC/HPC profile group, patients with a high HSC/HPC profile who had higher VEGF levels (p=0.012) and MVD (p=0.030) in tumours had significantly lower OS and RFS (p<0.0001). Based on Cox regression, a simplified model including CD133, CD44, Nestin and MVD was constructed and confirmed as an independent predictor for OS (p<0.0001) and RFS (p<0.0001), regardless of alpha-fetoprotein level, tumour stage and recurrence time (p<0.0001 for all). CONCLUSION:High expression levels of HSC/HPC biomarkers are related to tumour angiogenesis and poor prognosis of HCC. The simplified model based on the HSC/HPC and tumour angiogenesis profile can be used to classify patients with HCC with a high risk of tumour recurrence after surgery.

journal_name

Gut

journal_title

Gut

authors

Yang XR,Xu Y,Yu B,Zhou J,Qiu SJ,Shi GM,Zhang BH,Wu WZ,Shi YH,Wu B,Yang GH,Ji Y,Fan J

doi

10.1136/gut.2008.176271

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

953-62

issue

7

eissn

0017-5749

issn

1468-3288

pii

gut.2008.176271

journal_volume

59

pub_type

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