High expression levels of putative hepatic stem/progenitor cells biomarkers related to tumor angiogenesis and poor prognosis of hepatocellular carcinoma.
High expression levels of putative hepatic stem/progenitor cells biomarkers related to tumor angiogenesis and poor prognosis of hepatocellular carcinoma.
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与肿瘤血管生成和肝细胞癌不良预后相关的假定肝干/祖细胞生物标志物的高表达水平。
DOI：
10.1016/j.jamcollsurg.2009.06.220
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发表时间：
2009-09
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目的：探讨肝干/祖细胞（hepatic stem/progenitor cells，HSCs/HPCs）生物标志物在肝细胞癌（hepatocellular carcinoma，HCC）患者中的预后价值。在TMA分析中，HSC/HPC生物标志物细胞角蛋白19、ABCG 2、CD 133、Nestin、CD 44和血管生成剂CD 34、VEGF和PD-ECGF被确认为总生存期（OS）和/或无复发生存期（RFS）的显著预测因子。与低HSC/HPC谱组相比，具有高HSC/HPC谱的患者具有显著较低的OS和RFS（p<0.0001），表达较高的VEGF水平（p= 0.012）和微血管密度（MVD，通过CD 34免疫染色测定，p= 0.030）。基于考克斯回归，包括CD 133，CD 44，Nestin和MVD的简化模型被构建并被证实为OS（p<0.0001）和RFS（p<0.0001）的独立预测因子，而不考虑甲胎蛋白水平、肿瘤分期和复发时间（均p<0.0001）。基于HSCs/HPCs和肿瘤血管生成谱的简化模型可用于将HCC患者分类为术后肿瘤复发的高风险患者。
e22121Background:To investigate the prognostic values of putative hepatic stem/progenitor cells (HSCs/HPCs) biomarkers in hepatocellular carcinoma (HCC) patients.Methods:Fourteen biomarkers related with HSCs/HPCs or tumor angiogenesis were assessed by qRT-PCR and then validated by tissue microarrays (TMAs) in three independent cohorts of HCC patients underwent curative resection (n=67, 314 and 73).Results:Most of the biomarkers were found over-expressed in recurrent HCC patients by qRT-PCR. HSCs/HPCs biomarkers cytokeratin 19, ABCG2, CD133, Nestin, CD44 and angiogenesis agents CD34, VEGF and PD-ECGF, were confirmed as significant predictors for overall survival (OS) and/or relapse-free survival (RFS) in TMAs analysis. Compared with the low HSCs/HPCs profile group, patients with high HSCs/HPCs profile had significantly lower OS and RFS (p<0.0001), expressed higher VEGF levels (p= 0.012) and microvessel density (MVD, determined by CD34 immunostaining,p= 0.030). 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, tumor stage and recurrence time (p<0.0001 for all).Conclusions:High expression levels of HSCs/HPCs biomarkers are related to tumor angiogenesis and poor prognosis of HCC. The simplified model based on HSCs/HPCs and tumor angiogenesis profile can be used to classify HCC patients with high risk of tumor recurrence after operation.No significant financial relationships to disclose.