肿瘤干细胞标志EpCAM和CD133在人原发性肝癌中的表达及其对预后的临床意义

目的:检测肿瘤干细胞标志上皮细胞黏附分子(epithelial cell adhesion molecule,EpCAM)和CD133在原发性肝癌组织中表达的情况,探讨其与临床病理参数的关系及对肝癌预后的临床意义.方法:应用免疫组织化学方法检测70例人肝癌组织中EpCAM和CD133的表达情况.采用SPSS软件包进行相关分析和生存分析,研究EpCAM、CD133与肝癌临床病理特征及预后的关系.结果:CD133和EpCAM蛋白在肝癌组织中的阳性表达率明显高于癌旁组织(P＜0.01),癌旁组织中CD133未见表达.CD133在有血管浸润的肝癌组织中表达水平明显高于未浸润血管组(P＜0.05),而术前甲胎蛋白( alpha-fetoprotein,AFP)水平＞400 ng/mL、低分化和肿瘤浸润血管的癌组织中EpCAM表达水平明显高于相应对照组(P＜0.05).肝癌EpCAM蛋白表达与CD133蛋白表达呈正相关关系(P＜0.01).CD133表达强阳性的肝癌患者生存期明显短于CD133表达强度较低组.如果将EpCAM表达强阳性和中等阳性的肝癌患者合为一组,可见EpCAM中-强阳性表达的肝癌患者生存期短于EpCAM低表达者.通过术前AFP水平分层分析可见,术前AFP水平＞400 ng/mL组中EpCAM中-强阳性表达的患者生存期与低度阳性表达患者相比明显缩短.肿瘤数目、术前AFP水平、有无肿瘤包膜和CD133表达是影响肝癌预后的独立因素.结论:CD133和EpCAM可能参与肝癌发展的恶性进程,其高表达提示肝癌患者预后不良,因此推测EpCAM+ AFP+可能是肝癌恶性程度更高的标志.

Expressions of tumor stem cell markers EpCAM and CD133 in human primary hepatocellular carcinoma and their value in prognostic prediction

Objective:To investigate the expressions of tumor stem cell markers EpCAM (epithelial cell adhesion molecule) and CD133 proteins in human primary hepatocellular carcinoma, and to explore their relationships with clinicopathological features and the prognosis. Methods:The expressions of EpCAM and CD133 in liver cancer tissues from 70 patients with primary hepatocellular carcinoma were detected by immunohistochemistry. The survival analysis was performed, and the correlations of EpCAM and CD133 with the clinicopathological features and the prognosis were analyzed using SPSS (Statistical Package for the Social Sciences) software package 17.0. Results:The positive rates of CD133 and EpCAM proteins were both significantly higher in liver cancer tissues than those in paracancerous tissues (P < 0.01). Aberrant expression of CD133 was observed in the paracancerous tissues. The positive expression of CD133 was positively correlated with vascular invasion in liver cancer tissues (P < 0.05). The expression level of EpCAM in poorly differentiated liver cancer with vascular invasion in patients with preoperative AFP level over 400 ng/mL was significantly higher (P < 0.05). There was a positive correlation between EpCAM expression and CD133 expression (P < 0.01). The survival of patients with strongly positive expression of CD133 (or EpCAM) was inferior to that of patients with moderately-weakly positive expression of CD133 (or EpCAM). In the subgroup of preoperative AFP level over 400 ng/mL, the survival of patients with moderately-strongly positive expression of EpCAM was inferior to that of patients with weakly positive expression of EpCAM. The factors of the number of tumors, preoperative AFP level, tumor capsule and CD133 expression were independent predictors of prognosis of primary hepatocellular carcinoma. Conclusion:CD133 and EpCAM may be associated with the progression of primary hepatocellular carcinoma, and their high expression may indicate poor prognosis, thus it is suggested EpCAM (+) AFP (+) primary hepatocellular carcinoma subtype has features of high-grade malignancy.