D-D、PD-1/PD-L1、miR-16与肝癌经导管肝动脉化疗栓塞术治疗反应性的关系及预测术后复发的效能研究

Correlations between D-D,PD-1/PD-L1 and miR-16 with Response to TACE Treatment for Liver Cancer and Their Efficacies in Prediction of Recurrence after Operation

目的探讨D-二聚体(D-D)、程序性死亡受体-1(PD-1)/程序性死亡受体-配体1(PD-L1)、微小RNA-16(miR-16)与原发性肝癌经导管肝动脉化疗栓塞术(TACE)治疗反应性的关系及预测术后复发的效能。方法选取2017年4月—2020年5月我院收治的行TACE治疗的原发性肝癌169例,根据治疗反应性分为缓解组93例、非缓解组76例;随访3个月,将获访者151例分为复发组22例和未复发组129例。比较缓解组、非缓解组及复发组、未复发组D-D、PD-1/PD-L1通路指标、miR-16水平,分析D-D、CD8+PD-L1、miR-16与原发性肝癌治疗反应性的相关性及复发影响因素,并分析D-D、CD8+PD-L1、miR-16与三者联合预测复发的效能。结果与非缓解组比较,缓解组D-D、CD8+PD-L1水平降低,miR-16水平增高(P<0.05);D-D、CD8+PD-L1水平与治疗反应性呈负相关(r=-0.822、-0.742,P<0.01),miR-16水平与治疗反应性呈正相关(r=0.716,P<0.01)。与非复发组比较,复发组D-D、CD8+PD-L1水平增高,miR-16水平降低(P<0.05)。D-D>153.38μg/L、CD8+PD-L1>39.36%、miR-16≤0.91是原发性肝癌TACE后复发的危险因素(P<0.01)。D-D、CD8+PD-L1、miR-16及三者联合预测原发性肝癌TACE后复发的AUC依次为0.774、0.842、0.831、0.931(P<0.05)。结论D-D、PD-1/PD-L1、miR-16与原发性肝癌TACE治疗反应性及复发有关,D-D>153.38μg/L、CD8+PD-L1>39.36%、miR-16≤0.91是临床预测原发性肝癌TACE后复发提供客观、量化的数据。

Objective To investigate correlations between D-dimer(D-D),programmed death receptor-1(PD-1)/programmed death ligand-1(PD-L1)and microRNA-16(miR-16)with response of transcatheter arterial chemoembolization(TACE)treatment for liver cancer and their efficacies in prediction of recurrence after operation.Methods A total of 169 patients with primary liver cancer treated by TACE between April 2017 and May 2020 were selected,and they were divided into remission group(n=93)and non-remission group(n=76)according to therapeutic response.They were followed up for 3 months,and 151 respondents were divided into recurrence group(n=22)and non-recurrence group(n=129).The D-D,PD-1/PD-L1 pathway indicators and miR-16 levels were compared between remission and non-remission groups as well as recurrence and non-recurrence groups.Correlations between D-D,CD8+PD-L1 and miR-16 with response of the treatment for primary liver cancer and related influencing factors of recurrence were analyzed,and efficacies of D-D,CD8+PD-L1 and miR-16 and combination of the three indexes in prediction of recurrence were analyzed.Results Compared with those in non-remission group,D-D and CD8+PD-L1 levels were significantly lower,while miR-16 levels was significantly higher(P<0.05);D-D and CD8+PD-L1 levels were negatively correlated with treatment response(r=-0.822,-0.742,P<0.01),while miR-16 level was positively correlated with treatment response in remission group(r=0.716,P<0.01).Compared with those in non-recurrence group,D-D and CD8+PD-L1 levels were significantly higher,while miR-16 level was significantly lower in recurrence group(P<0.01).D-D more than 153.38μg/L,CD8+PD-L1 more than 39.36%and miR-16 less than or equal to 0.91 were all risk factors of recurrence in patients with primary liver cancer after TACE(P<0.05).Area under curve(AUC)values of D-D,CD8+PD-L1,miR-16 and combination of the three indexes in prediction of recurrence after TACE were 0.774,0.842,0.831 and 0.931 respectively(P<0.05).Conclusion D-D,PD-1/PD-L1 and miR-16 are related to the response of TACE treatment for liver cancer and recurrence after TACE.When D-D more than 153.38μg/L,CD8+PD-L1 more than 39.36%and miR-16 less than or equal to 0.91,it may provide an objective and quantitative data for clinical prediction of recurrence in patients with liver cancer after TACE.