Abstract:

Objective To investigate the value of serum AFP，PIVKA- Ⅱ and miR-21 in hepatocellular carcinoma（HCC）. Methods A total of 90 patients with compensatory cirrhosis who hospitalized in the Department of Hepatology，Tianjin Second People's Hospital from December 2017 to June 2018 wereenrolledAll patients underwent liver（gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid，Gd - EOB - DTPA ）enhanced MRI. The patients were divided into three groups ：HCC group，high-grade dysplastic nodules（HGDN）group and regenerative nodule（RN）group，and each group had 30 patients. Their serum samples were collected and the serum levels of PIVKA- Ⅱ，AFP and miR-21 were measured. Kruskal-wallis H test was used to compare thedifferences between groups. Significance levels were corrected by Bonferroni method and pairwise comparisons were made .The index of AFP，PIVKA- Ⅱ and miR-21 was analyzed by binary logistic regression，and the diagnostic value of the above indexes for HCC was evaluated by the areas under the receiver operating characteristic curve （AUC）. Results There were no difference in AFP and PIVKA- Ⅱ level between RN and HGDN group. However， AFP and PIVKA- Ⅱ levels in HCC group were higher than those in the other two groups，and the difference was statistically significant（adjusted P ＜ 0.05）. The level of miR-21 increased gradually from the RN group，HGDN group to HCC group. There were significant differences in the serum levels of miR-21 among the three groups （adjusted P ＜ 0.05）. When measured alone，the specificity and sensitivity of AFP were 91.7% and 53.3% in the diagnosis of HCC. The specificity and sensitivity of PIVKA- Ⅱ were 93.3% and 66.7% and the sensitivity and specificity of miR-21 were 97.1% and 85.0%，respectively. The sensitivity and specificity of the combined model of APR were 93.3% and 91.7%. The AUC of AFP，PIVKA- Ⅱ，miR-21 and APR were 0.756、0.873、0.953 and 0.963，respectively. Among them，APR had the highest AUROCs. Conclusion Serum AFP，PIVKA- Ⅱ and miR-21 have a high clinical value in the diagnosis of HCC，but each has its own limitation when measured alone. The combination of the three makers is beneficial to the diagnosis and screening of HCC. 

Key words:

Hepatocellular carcinoma , Alpha-fetoprotein , Protein induced by vitamin K absenceorantagonist- Ⅱ, MicroRNA, High-grade dysplastic nodules, Diagnosis

摘要：

目的 探讨血清甲胎蛋白（alpha-fetoprotein，AFP）、异常凝血酶原（protein induced by vitamin K absence antagonist- Ⅱ，PIVKA- Ⅱ）和微小 RNA-21（microRNA-21，miR-21）检测对肝细胞癌 （hepatocellular carcinoma，HCC）的诊断意义。方法 筛选 2017 年 12 月至 2018 年 6 月在天津市第二人民医院住院的代偿期肝硬化患者，经肝脏钆塞酸二钠增强 MRI 检查，纳入临床诊断为 HCC、肝硬化伴高度异型增生结节（high-grade dysplastic nodules，HGDN）及肝硬化伴再生结节（regenerative nodule，RN）的患者共 90 例，分为 HCC 组、HGDN 组及 RN 组，每组 30 例。收集血清检测 AFP、PIVKA- Ⅱ及 miR-21水平。采用 Kruskal-Wallis H 检验比较组间差异，Bonferroni 法校正显著性水平后进一步两两比较，通过二元 logistic 回归建立三种指标联合模型 APR，采用受试者工作特征曲线下面积（the area under the receiveroperating characteristic curve，AUC）评估 AFP、PIVKA- Ⅱ、miR-21 及联合模型 APR 对 HCC 的诊断效能。结果 AFP、PIVKA- Ⅱ水平在 RN 组和 HGDN 组间无差异，但 HCC 组高于 HGDN 组和 RN 组，差异有统计学意义（校正后 P ＜ 0.05）；miR-21 水平在 RN 组、HGDN 组及 HCC 组间逐渐升高，差异有统计学意义（校正后 P ＜ 0.05）。 单项检测诊断 HCC 时，AFP 的特异度为 91.7%，敏感度为 53.3% ；PIVKA- Ⅱ的特异度为 93.3%，敏感度为 66.7% ；miR-21 的敏感度为 97.1%，特异度为 85.0%。三种指标联合模型 APR 的敏感度和特异度分别为 93.3%、91.7%。AFP、PIVKA-Ⅱ、miR-21 及联合模型 APR 对 HCC 诊断的 AUC 分别 为 0.756、0.873、0.953 和 0.963。结论 血清 AFP、PIVKA-Ⅱ、miR-21 对 HCC 有较高的诊断价值，但单项检测时各有不足，三者联合检测有助于 HCC 的诊断筛查。

关键词:

原发性肝癌 ；甲胎蛋白 ；异常凝血酶原 ；微小 RNA-21 ；高度异型增生结节 ； 诊断 ,