Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development.
Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development.
复制标题
羧肽酶4和干细胞标记的表达与它们在肝癌发育中的临床意义之间的关联。
DOI：
10.7150/jca.17060
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发表时间：
2017
影响因子：
3.9
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Sun L;Guo C;Burnett J;Pan J;Yang Z;Ran Y;Sun D
肝癌的发展会经历从慢性炎症性肝病、肝硬化到肿瘤形成的连续过程。在这些病理生理变化过程中，异常的肝脏微环境可能诱导肝细胞死亡、异常增殖并产生癌症干细胞。金属羧肽酶（MCPs）参与包括炎症、纤维化和干细胞微环境形成在内的多种生物学功能。本研究旨在评估羧肽酶4（CPA4）在肝炎、肝硬化和肝癌组织中的表达，并揭示其在肝癌进展中的临床意义。我们首先发现肝癌患者组织中的CPA4水平显著高于其他三组。然后，在100例肝癌样本中有57例（57%）观察到CPA4水平升高，且与肿瘤分级和分期显著相关。我们还通过随访数据（n = 100）确定了CPA4异常升高与包括CD90、甲胎蛋白（AFP）和CD34在内的干细胞标志物过表达之间存在显著正相关。进一步的卡普兰 - 迈耶分析证实，高水平的CPA4和CD90是总体生存率低的重要预测因子。多变量考克斯回归模型显示，CPA4是肝癌患者的一个独立预后因素。本研究首次表明，CPA4高表达与肝癌发生密切相关，并可能作为肝癌的一个独立不良预后因素。
The development of liver cancer would undergo a sequential progression from chronic inflammatory liver disease, cirrhosis to neoplasia. During these pathophysiological changes, abnormal liver microenvironment might induce the hepatocytes to die, abnormally proliferate and initiate cancer stem cells. Metallocarboxypeptidases (MCPs) involved in multiple biological functions including inflammation, fibrosis and stem cell niche formation. This study aimed to evaluate the expression of carboxypeptidase 4 (CPA4) in hepatitis, liver cirrhosis and liver cancer tissues, and revealed its clinical significance in liver cancer progression. We firstly found that the CPA4 levels in tissues were significantly higher in liver cancer patients than those in other three groups. Then, elevated levels of CPA4 was observed in 57/100 (57%) liver cancer samples, and significantly correlated with Grade and Stage. We also identified a significant positive correlation between aberrant elevation of CPA4 and overexpression of stem cell markers including CD90, AFP and CD34 with follow-up data (n=100). Further Kaplan-Meier analysis confirmed that high levels of CPA4 and CD90 were significant predictors of poor overall survival. Multivariate Cox regression model showed that CPA4 was an independent prognostic factor for patients with liver cancer. This study demonstrated for the first time that high CPA4 expression was closely correlated with hepatocarcinogenesis, and might be used as an independent poor prognostic factor in liver cancer.