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

作者：Xin‐Rong Yang, Yang Xu, Bing Yu, Jian Zhou, Shuang–Jian Qiu, Guo‐Ming Shi, Bo-Heng Zhang, Wei‐Zhong Wu, Ying-Hong Shi, Boting Wu, Guo-Huan Yang, Yuan Ji, Jia Fan · 发表于：Gut · 年份：2010 · DOI：10.1136/gut.2008.176271 · 被引用次数：272 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Angiogenesis and VEGF in Cancer、Cancer Cells and Metastasis

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/H...