肝细胞癌患者外周血中Midkine、CTCs的表达水平及临床意义

目的:观察中期因子（Midkine）、循环肿瘤细胞（CTCs）在肝细胞癌患者外周血中的表达水平，并研究它们与肝癌临床病理参数之间的关系。方法:收集我院96例原发性肝癌患者临床资料为肝癌组，40例健康体检组作为对照组。采用酶联免疫吸附法（ELISA）和电化学发光法检测Midkine水平，采用阴性富集法检测CTCs计数。分析Midkine、CTCs在肝细胞癌患者外周血中的表达与临床病理参数之间的关系以及肝细胞癌患者外周血Midkine表达与CTCs表达的相关性。结果:肝癌组外周血Midkine的表达水平显著高于对照组（P＜0.001）；肝癌组外周血中CTCs阳性检出率(70.8%,68/96)显著高于对照组(7.5%,3/40)（P＜0.001）。肝癌患者外周血Midkine表达在肿瘤大小、血管侵犯、Child-pugh分级、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。肝癌患者外周血CTCs表达在血管侵犯、Child-pugh分级、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。本研究结果显示，96例肝癌患者中，上皮型CTCs阳性率为31.3%，间质型CTCs阳性率为44.8%，混合型CTCs阳性率为67.7%。三种CTCs类型在肿瘤大小、血管侵犯、AFP水平、BCLC分期及Edmondson-Steiner分级均有显著差异（P＜0.05）。Spearman相关性分析得出，外周血Midkine表达与CTCs表达呈正相关（r=0.531，P=0.007）。结论:肝细胞癌患者外周血Midkine与CTCs的表达均高于正常组，Midkine与CTCs可能在肝癌的发生发展中发挥作用，且两者在肝细胞癌患者外周血中的表达呈正相关。

Expression levels and clinical significance of Midkine and CTCs in peripheral blood of patients with hepatocellular carcinoma

Objective:To observe the expression levels of Midkine and circulating tumor cells (CTCs) in peripheral blood of patients with hepatocellular carcinoma (HCC),and to investigate the relationship between Midkine and CTCs and clinicopathological parameters of HCC.Methods:Clinical data of 96 patients with primary liver cancer in our hospital were collected as liver cancer group and 40 healthy patients as control group.Midkine levels were detected by enzyme-linked immunosorbent assay (ELISA) and electrochemical luminescence,and CTCs counts were detected by negative enrichment method.The relationship between Midkine and CTCs expression in peripheral blood of hepatocellular carcinoma patients and clinicopathological parameters,as well as the correlation between Midkine expression and CTCs expression in peripheral blood of hepatocellular carcinoma patients were analysed.Results:The expression level of Midkine in peripheral blood of liver cancer group was significantly higher than that of control group (P＜0.001).The CTCs positive rate of 68 cases in the liver cancer group was significantly higher than that of the control group (7.5%) (P＜0.001).The expression of Midkine in peripheral blood of liver cancer patients was significantly different in tumor size,vascular invasion,Child-pugh grade,AFP level,BCLC stage,and Edmondson-Steiner grade (P＜0.05).The expression of CTCs in peripheral blood of liver cancer patients was significantly different in vascular invasion,Child-pugh grade,AFP level,BCLC stage and Edmondson-Steiner grade (P＜0.05).The results of this study showed that among the 96 patients with liver cancer,the positive rate of epithelial CTCs was 31.3%,stromal CTCs was 44.8%,and mixed CTCs was 67.7%.The three CTCs types showed significant differences in tumor size,vascular invasion,AFP level,BCLC stage and Edmondson-Steiner grade (P＜0.05).Spearman correlation analysis showed that Midkine expression in peripheral blood was positively correlated with CTCs expression (r=0.531,P=0.007).Conclusion:The expression levels of Midkine and CTCs in peripheral blood of hepatocellular carcinoma patients were higher than that of the normal group.Midkine and CTCs may play a role in the occurrence and development of hepatocellular carcinoma,and the expressions of Midkine and CTCs in peripheral blood of hepatocellular carcinoma patients were positively correlated.