阿帕替尼联合经动脉导管灌注化疗栓塞术治疗原发性肝癌的临床效果及对患者免疫功能的影响

Clinical efficacy of apatinib combined with transcatheter arterial chemoembolization on primary liver cancer and its influence on immune function

目的探讨阿帕替尼联合经动脉导管灌注化疗栓塞术(TACE)治疗原发性肝癌的临床效果及对患者免疫功能的影响。方法回顾性分析2017年6月至2019年2月湖南中医药高等专科学校附属第一医院收治的92例原发性肝癌患者的临床资料。根据是否联合应用阿帕替尼将患者分为观察组和对照组,各46例。对照组给予TACE治疗,观察组在对照组基础上联合阿帕替尼口服治疗。比较2组患者临床疗效、免疫功能指标、血清热休克蛋白90α(HSP90α)、肿瘤蛋白D52(TPD52)、高迁移率族蛋白B2(HMGB2)表达水平、不良反应发生情况及随访结果。结果观察组客观缓解率、疾病控制率均高于对照组[47.8%(22/46)比26.1%(12/46)、80.4%(37/46)比65.2%(30/46)](均P<0.05)。治疗后1、3、6个月2组CD_(3)^(+)、CD_(4)^(+)水平均高于治疗前、且观察组均高于对照组,CD_(8)^(+)水平均低于治疗前、且观察组均低于对照组[CD_(8)^(+)组间比较:(26.7±5.7)%比(30.8±6.7)%、(23.8±3.4)%比(30.9±6.8)%、(20.3±2.8)%比(26.4±8.2)%],差异均有统计学意义(均P<0.05);2组血清HSP90α、HMGB2水平均低于治疗前、且观察组均低于对照组,TPD52表达水平均高于治疗前、且观察组均高于对照组,差异均有统计学意义(均P<0.05)。2组白细胞减少、腹痛、胃肠道反应、发热、肝损伤等不良反应发生率比较,差异均无统计学意义(均P>0.05)。随访1年期间,观察组死亡率明显低于对照组[10.9%(5/46)比21.7%(10/46)](P=0.026)。结论阿帕替尼联合TACE治疗原发性肝癌效果确切,可显著提高患者免疫功能,改善其血清HSP90α、TPD52、HMGB2表达,抑制肿瘤进展,且不增加不良反应发生率。

Objective To investigate the clinical efficacy of apatinib combined with transcatheter arterial chemoembolization(TACE)on primary liver cancer and its influencing on immune function.Methods From June 2017 to February 2019,clinical data of 92 patients with primary liver cancer in the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine were retrospectively analyzed.According to the application of alpatinib,patients were divided into control group and observation group,with 46 cases in each group.The control group was treated with TACE,and the observation group was treated with apatinib on the basis of the control group.The clinical efficacy,immune function,serum levels of heat shock protein 90α(HSP90α),tumor protein D52(TPD52),high mobility group protein B2(HMGB2),adverse effects and follow-up outcomes were compared between the two groups.Results The objective response rate and disease control rate in the observation group were higher than those in the control group[47.8%(22/46)vs 26.1%(12/46),80.4%(37/46)vs 65.2%(30/46)](both P<0.05).The levels of CD_(3)^(+) and CD+4 in both groups 1,3 and 6 months after treatment were higher than those before treatment,and the levels in the observation were higher than those in the control group;the levels of CD_(8)^(+) in both groups were lower than those before treatment,and the levels in the observation group were lower those in the control group[CD_(8)^(+):(26.7±5.7)%vs(30.8±6.7)%,(23.8±3.4)%vs(30.9±6.8)%,(20.3±2.8)%vs(26.4±8.2)%](all P<0.05).Serum levels of HSP90αand HMGB2 in both groups 1,3 and 6 months after treatment were lower than those before treatment,and the levels in the observation group were lower than those in the control group;levels of TPD52 in both groups were higher than those before treatment,and the levels in the observation group were higher than those in the control group(all P<0.05).The incidences of adverse reactions such as leucopenia,abdominal pain,gastrointestinal reaction,fever and hepatic injury were not statistically significant between the two groups(all P>0.05).During 1 year of follow-up,the mortality in the observation group was lower than that in the control group[10.9%(5/46)vs 21.7%(10/46)](P=0.026).Conclusions Apatinib combined with TACE is effective on treating primary liver cancer.It can significantly improve the immune function,regulate serum levels of HSP90α,TPD52 and HMGB2,inhibit tumor progression,and does not increase the incidence of adverse reactions.