超声造影联合miR-599水平在原发性肝癌TACE预后评估中的价值

Value of contrast-enhanced ultrasound combined with miR-599 level for prognostic evaluation of primary hepatic carcinoma treated with TACE

目的:探讨超声造影(CEUS)联合血清微小RNA-599(miR-599)评估原发性肝癌(PHC)经导管动脉栓塞(TACE)术后疗效的价值。方法:采用回顾性研究方法,选取接受TACE治疗的80例PHC患者进行研究分析。根据实体瘤疗效标准(RECIST)将患者分为有效组54例和无效组26例,分别于TACE后第7天、14天、1月、2月时采用CEUS检查患者的肿瘤病灶灭活率,于术前及术后第7天、14天、1月、2月时检查患者血清miR-599水平,以患者TACE术后2月时的数字减影血管造影检查结果作为金标准,计算CEUS评估疗效的价值,并采用单因素分析方法及多因素Logistic回归模型分析血清miR-599与PHC患者TACE治疗效果的关系。结果:80例接受TACE治疗的PHC患者,在接受治疗2月后进行评价,其中完全缓解9例、部分缓解45例、疾病稳定22例、疾病进展4例;有效组患者的年龄、体质量指数、TACE次数、Childpugh分级、HBsAg结果与无效组比较,差异均无统计学意义(P>0.05);有效组患者与无效组患者的术前甲胎蛋白水平、病灶数目、最大病灶直径、病理学分期、是否使用索菲拉尼的情况比较,差异均具有统计学意义(P<0.05);术后1月时有效组的病灶灭活率为66.67%,术后2月时有效组患者的病灶灭活率为94.44%,有效组在术后1月、2月时的病灶灭活率显著高于无效组患者(P<0.05);无效组患者在术前及术后第7天、14天、1月、2月的血清miR-599水平均显著低于有效组患者(P<0.05);Logistic回归模型显示:术前miR-599低水平、术前AFP≥400μg/L、病灶直径≥5.0 cm、病理学分期为ⅢA期是TACE治疗PHC患者疗效不佳的独立危险因素(P<0.05),使用索菲拉尼有利于提高TACE治疗PHC患者的效果(P<0.05)。结论:应用TACE治疗的PHC患者,采用CEUS动态观察病灶变化情况,能较为准确地评估其临床治疗效果,而血清miR-599水平越低的PHC患者TACE治疗效果越差,可将CEUS病灶观察结果与血清miR-599检测结合,对PHC患者TACE的治疗效果进行综合评价。

Objective To explore the value of contrast-enhanced ultrasound(CEUS) combined with serum microRNA-599(miR-599) in evaluating the therapeutic efficacy of transcatheter arterial chemoembolization(TACE) in primary hepatic carcinoma(PHC).Methods A retrospective study was conducted on 80 PHC patients receiving TACE.According to response evaluation criteria in solid tumors(RECIST),the patients were divided into effective group(n=54) and ineffective group(n=26).CEUS was used to obtain the tumor lesion inactivation rate on the 7th day,14th day,1st month,and 2nd month after TACE;and the serum miR-599 level was measured before TACE and on the 7th day,14th day,1st month,and 2nd month after TACE.The results of digital subtraction angiography at the 2nd month after TACE were taken as the gold standard to assess the value of CEUS in evaluation of therapeutic efficacy.The relationship between serum miR-599 and TACE outcome in PHC was analyzed using univariate analysis and multivariate Logistic regression model.Results The evaluation at 2 months after TACE showed that among 80 PHC patients treated with TACE,there were 9 cases of complete response,45 of partial response,22 of stable disease,and 4 of progressive disease.The differences in age,body mass index,TACE frequency,Childpugh grade,and HBsAg result between effective group and ineffective group were trivial(P>0.05);while the two groups differed significantly in preoperative alpha-fetoprotein level,number of lesions,maximum lesion diameter,pathological staging,and whether to use Sofilanide(P<0.05).The lesion inactivation rates at the 1st and 2nd months after TACE were66.67% and 94.44% in effective group,significantly higher than those in ineffective group(P<0.05).The serum miR-599levels were significantly lower in ineffective group than in effective group preoperatively,and 7 days,14 days,1 month,2 month postoperatively(P<0.05).The results of Logistic regression model showed that preoperative low miR-599 level,preoperative AFP ≥ 400 μg/L,lesion diameter ≥ 5.0 cm,and pathological staging of stage IIIA were independent risk factors for poor efficacy of TACE in PHC(P<0.05).Sofilanib could improve the efficacy of TACE in treating PHC(P<0.05).Conclusion For PHC patients undergoing TACE,the dynamic observation of lesion changes using CEUS can accurately evaluate the therapeutic effect in clinic.However,primary tumor patients with lower serum miR-599 level have poor response to TACE.Lesion observation using CEUS can be combined with serum miR-599 measurement to comprehensively evaluate the treatment outcome in PHC patients.