原发性肝癌患者CTCs与CD4^+/CD8^+、NLR、TTV及肿瘤分期的相关性研究

Relationship of CTCs with CD4^+/ CD8^+,NLR,TTV and tumor stage in patients with primary hepatocellular carcinoma

目的:探讨原发性肝癌患者外周血循环肿瘤细胞(CTCs)与T细胞亚群CD4^+/CD8^+比值、中性粒细胞与淋巴细胞比值(NLR)、肿瘤总体积(TTV)及肿瘤分期的关系。方法:收集80例原发性肝癌患者外周血,采用益善生物技术公司使用的"免疫去除结合纳米过滤法"Can PatrolTM行CTCs检测。同时使用流式细胞术检测外周血中CD4+T细胞和CD8^+T细胞数量;收集患者外周血中性粒细胞数、淋巴细胞数、肿瘤最大直径及肿瘤分期等临床病理参数。计算出外周血CD4^+/CD8^+比值、NLR及TTV。根据CD4^+/CD8^+平均值及TTV、NLR中位数将CD4+/CD8+比值、TTV和NLR分为高、低2组;根据肝癌第7版TMN分期标准将患者分为I+II期和III+IV期2组。分别比较CTCs在2组中的差别。结果:高CD4^+/CD8^+比值组外周血CTCs数及间质型CTCs数明显低于低CD4^+/CD8^+比值组(P<0.05)。高TTV组外周血的CTCs数、间质型CTCs数及混合型CTCs数明显高于低TTV组(P<0.05);肿瘤分期I、II期组外周血的CTCs数、间质型CTCs数及混合型CTCs数明显低于III、IV期组(P<0.05)。高NLR组与低NLR组外周血的CTCs数、间质型CTCs数、混合型CTCs数和上皮型CTCs数间的差异无统计学显著性。结论:原发性肝癌患者外周血中存在CTCs;外周血CTCs与T细胞免疫、TTV及肿瘤分期有显著相关:T细胞免疫越差、TTV越大及肿瘤分期越晚,外周血的CTCs越多。

AIM： To explore the relationship of circulating tumor cells（ CTCs） with CD4^＋/ CD8^＋,neutrophil-to-lymphocyte ratio（ NLR）,total tumor volume（ TTV） and tumor stage in the patients with primary hepatocellular carcinoma. METHODS： We selected 80 cases of histologically diagnosed primary hepatocellular carcinoma in the study.The method of Can PatrolTMwas used,which was developed by Sur Exam biotechnology company to identify CTCs in the blood. CD4^＋T cells and CD8^＋T cells were counted by flow cytometry. The patients were divided into 2 groups according to the levels of CD4^＋/ CD8^＋ ratio,NLR and TTV. The patients were also divided into Ⅰ ＋ Ⅱstage group and Ⅲ ＋ Ⅳstage group according to the seventh edition of TMN staging criteria. RESULTS： The numbers of peripheral blood CTCs and mesenchymal CTCs in high CD4^＋/ CD8^＋ ratio group were significantly lower than those in low CD4^＋/ CD8^＋ratio group（ P〈0. 05）. The numbers of peripheral blood CTCs,mesenchymal CTCs and hybrid CTCs in high TTV group were significantly higher than those in low TTV group（ P〈0. 05）. The numbers of peripheral blood CTCs,mesenchymal CTCs and hybrid CTCs in I ＋ II stage group were significantly lower than those in III ＋ IV stage group（ P〈0. 05）. The numbers of peripheral blood CTCs,mesenchymal CTCs,hybrid CTCs and epithelial CTCs between high NLR group and low NLR group had no statistical difference. CONCLUSION： CTCs exist in the peripheral blood of the patients with primary hepatocellular carcinoma. The peripheral blood CTCs have significant correlations with TTV,tumor stage and T-cell immunity. The worse cell immune function,the larger TTV and the later tumor stage a patient has,the more the peripheral blood CTCs are.