摘要目的 探讨外周血中TEMs占CD14+CD16+单核细胞百分比在AFP阴性及肿瘤体积≤3 cm肝细胞癌(HCC)中的诊断价值.方法 通过流式细胞术检测肝细胞癌组82例、肝硬化(LC)组29例、慢性乙型肝炎(CHB)组28名和健康对照(NC)组31例外周血TEMs占CD14+CD16+单核细胞百分比,同时采用美国雅培i2000微粒子化学发光免疫分析仪检测其血浆AFP水平.多组比较采用Kruskal-Wallis H 检验,两两比较用Mann-Whitney U 检验,率的比较采用χ2检验,Spearman秩相关分析TEMs与AFP相关性,分析TEMs诊断HCC、AFP阴性及肿瘤体积≤3 cm肝细胞癌的受试者工作曲线下面积(ROC-AUC)、敏感度及特异度.结果 在HCC组、AFP阴性肝癌组及肿瘤体积≤3 cm肝细胞癌组中TEMs均高于LC、CHB及NC组,P均小于0.05.TEMs和AFP诊断HCC的ROC-AUC分别为0.701(95%CI 0.626~0.768)、0.712(95% CI 0.638~0.779).当TEMs和AFP的最佳cut-off值设为4.95%和20 μg/L时,其诊断HCC的敏感度分别为71.95%和45.12%,特异度分别为70.45%和85.23%,TEMs的敏感度显著高于AFP(χ2=12.16, P=0.000),但AFP的特异度高于TEMs(χ2=5.57,P=0.018).采用TEMs/AFP方案其诊断HCC敏感度最高(89.02%),采用TEMs+AFP方案时诊断特异度最高(93.18%).TEMs 与AFP对26例肿瘤体积≤3 cm HCC的ROC-AUC无显著性差异(0.776 vs 0.645,Z=1.805,P=0.071).采用TEMs/AFP方案其诊断肿瘤体积≤3 cm HCC灵敏度最高(84.62%),采用TEMs+AFP方案时诊断特异度最高(93.18%).TEMs对45例AFP阴性HCC患者鉴别诊断的ROC-AUC为0.739(95%CI 0.648~0.829),其诊断灵敏度和特异度分别为80.0%和70.45%.Spearman秩相关分析82例HCC患者TEMs与AFP水平显示两指标间无相关性(r=-0.169,P=0.129).结论 TEMs对AFP阴性和肿瘤体积≤3 cm肝细胞癌有一定诊断价值,且两指标在诊断HCC患者时可以互相补充.

abstractsObjective To evaluate the diagnosis value of the percentage of Tie 2-expressing monocytes(TEMs)in CD14+CD16+monocytes of peripheral blood from hepatocellular carcinoma(HCC) patients with negative AFP and tumor size≤3 cm.Methods Flow Cytometry(FCM)was used to determine the percentage of TEMs in CD14+CD16+monocytes of peripheral blood from patients with HCC(n=82), liver cirrhosis(n=29), chronic hepatitis B(n=28), and healthy controls(n=31).Abbott i2000 microparticle chemiluminescence immunoassay analyzer was used to determine the plasma alpha -fetoprotein (AFP)levels.The difference among multi groups was analyzed by the Kruskal-Wallis H test.Two independent groups were analyzed by the Mann-Whitney U test.The chi-square test was used in the rate comparison.The correlation between TEMs and AFP was analyzed by Spearman rank correlation analysis. Morever, the areas under the receiver operating characteristic curves(ROC-AUC), sensitivity and specificity of TEMs or AFP in differentiating HCC, HCC with AFP negative or tumor size≤3 cm were analyzed.Results The percentage of TEMs in CD14 +CD16 +monocytes of peripheral blood from HCC or HCC with negative AFP or HCC with tumor size≤3 cm was significantly higher than that in patients with liver cirrhosis,chronic hepatitis B and healthy controls(P<0.05).ROC-AUC of TEMs and AFP in the diagnosis of HCC were 0.701(95% CI 0.626-0.768)and 0.712(95% CI 0.638-0.779) respectively.When the cut-off values of TEMs and AFP were 4.95%and 20 μg/L,the sensitivities of TEMs and AFP were 71.95%and 45.12%,and the specificities of TEMs and AFP were 70.45%and 85.23%. The sensitivity of TEMs in the diagnosis of HCC was significantly higher than that of AFP(χ2=12.16,P=0.000).The specificity of AFP was significantly higher than that of TEMs(χ2=5.57,P=0.018).There was a highest sensitivity(89.02%)in TEMs/AFP method,and there was a highest specificity(93.18%) in TEMs+AFP method in the diagnosis of HCC.There was no significant difference between the ROC-AUC for the TEMs and the AFP in the diagnosis of 26 patients with tumor size≤3 cm HCC(0.776 vs 0.645,Z=1.805,P=0.071),TEMs/AFP had the highest sensitivity(84.62%),while TEMs+AFP had the highest specificity(93.18%)in the diagnosis of tumor size≤3cm HCC.The ROC-AUC for the TEMs in the diagnosis of 45 patients with AFP negative HCC was 0.739(95%CI 0.648-0.829).The sensitivity and specificity of TEMs were 80.0% and 70.45% respectively.There was no correlation between the level of plasma AFP and the percentage of TEMs(r=-0.169, P=0.129)determined by Spearmans rank correlation coefficient.Conclusions TEMs is valuable in the diagnosis of HCC with negative AFP and tumor size≤3cm,and the two tests of TEMs and AFP can complement each other in the diagnosis of patients with HCC.