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目的检测肝癌患者外周血中循环肿瘤细胞(CTC),探讨CTC检测在肝癌诊断和治疗监测中的应用价值。方法选择肝癌患者27例纳入肝癌组,另选30例健康体检者为对照组。采集两组外周血,用差减富集技术富集CTC,荧光原位杂交技术选择CTC;采用电化学发光法检测两组血清肿瘤标志物甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原199(CA199)。比较CTC、AFP、CEA、CA199检测诊断肝癌的敏感性、特异性、约登指数。分析CTC检测结果与索拉菲尼靶向治疗效果的关系。结果肝癌组CTC阳性22例(81.5%),对照组均未检出CTC,两组检出率相比,P<0.05。肝癌患者中均检出C亚群肿瘤细胞,肝胆管细胞癌患者检出A、B、C亚群肿瘤细胞。所有CTC阳性患者外周血中均检出多倍体CTC,以三倍体肿瘤细胞数量最多(59.8%)。肝癌组中,AFP阳性17例、CEA阳性10例、CA199阳性11例,对照组分别为2、1、0例。CTC检测诊断肝癌的约登指数均高于三项肿瘤标志物检测(P均<0.05)。肝癌组中10例坚持服用索拉菲尼,8例治疗过程中CTC数量未有明显变化,疗效评价为SD,2例治疗前CTC总数较高患者(>15/7.5 m L)在索拉菲尼治疗1个周期后有明显下降(<5/7.5 m L),但疗效评价也为SD。结论利用差减富集技术可有效检出肝癌患者外周血中的CTC。CTC检测较常用肿瘤标志物检测在肝癌诊断方面更有优势,也有助于评估肝癌患者靶向治疗的效果。
Objective To detect circulating tumor cells (CTCs) in peripheral blood of patients with hepatocellular carcinoma (HCC) and to explore the value of CTC detection in the diagnosis and treatment of HCC. Methods Twenty-seven patients with hepatocellular carcinoma (HCC) were enrolled in the HCC group and 30 healthy subjects were selected as the control group. CTCs were collected by differential subtractive enrichment and CTCs were selected by fluorescence in situ hybridization. AFP, CEA, Carbohydrate antigen 199 (CA199). CTC, AFP, CEA, CA199 detection of liver cancer sensitivity, specificity, Youden index. To analyze the relationship between CTC test results and sorafenib targeted therapy. Results CTC positive in HCC group was 22 (81.5%), but CTC was not detected in the control group, P <0.05. C subgroup of tumor cells were detected in patients with hepatocellular carcinoma, and tumor cells in subgroup A, B and C were detected in patients with hepatobiliary and cholangiocarcinoma. Polyploid CTCs were detected in peripheral blood of all CTC-positive patients, with the highest number of triploid tumor cells (59.8%). Liver cancer group, AFP positive in 17 cases, CEA positive in 10 cases, CA199 positive in 11 cases, the control group were 2,1,0 cases. The Youden index of CTC test for detecting HCC was higher than that of three tumor markers (all P <0.05). Ten patients in the hepatocellular carcinoma group were treated with sorafenib. There was no significant change in the number of CTCs in 8 patients, and the therapeutic effect was evaluated as SD. Two patients with higher CTCs before treatment (> 15 / 7.5 m L) After 1 cycle of treatment, there was a significant decrease (<5 / 7.5 m L), but the efficacy evaluation was also SD. Conclusion The differential subtractive enrichment technique can effectively detect the CTC in the peripheral blood of patients with liver cancer. CTC test more commonly used in tumor markers detection of liver cancer more advantages, but also help to assess the effect of targeted therapy in patients with liver cancer.