肝癌患者NOP2基因状态对免疫治疗疗效及预后的影响  

Effects of NOP2 gene status on immunotherapy efficacy and prognosis of patients with liver cancer

作　　者：李哲恒 陈圣雄[2] 宋玉涛 郝子佳 王文斌[2] 贵英斌 Li Zheheng;Chen Shengxiong;Song Yutao;Hao Zijia;Wang Wenbin;Gui Yingbin(Department of Hepatobiliary Surgery,People’s Hospital of Dingzhou,Hebei Dingzhou 073000,China;Department of Hepatobiliary Surgery,The Second Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China;Department of Dermatology,Shijiazhuang Hospital of Traditional Chinese Medicine,Hebei Shijiazhuang 050000,China)

机构地区：[1]河北省定州市人民医院肝胆外科,河北定州073000 [2]河北医科大学第二医院肝胆外科,河北石家庄050000 [3]石家庄市中医院皮肤科,河北石家庄050000

出　　处：《中国肝脏病杂志(电子版)》2024年第4期38-47,共10页Chinese Journal of Liver Diseases:Electronic Version

基　　金：河北省医学科学研究课题计划(20220086)。

摘　　要：目的分析肝癌患者NOP2基因状态对免疫治疗疗效及预后的影响。方法以2017年6月至2020年6月于河北省定州市人民医院住院治疗的157例肝癌患者为研究对象,根据NOP2基因状态分为NOP2突变组(56例)和NOP2野生组(101例)。比较两组患者的临床资料[包括性别、年龄、体重指数(body mass index,BMI)、中国肝癌分期(China clinic liver cancer staging,CNLC staging)、肝功能Child-Pugh分级、东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分等]、免疫治疗疗效[客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)]及预后情况。对患者随访3年,记录患者的总生存期(overall survival,OS)和无进展生存期(progress free survival,PFS)。通过Kaplan-Meier法绘制生存曲线分析不同NOP2基因状态肝癌患者的PFS和OS。通过单因素及多因素Cox回归分析影响患者PFS和OS的因素。建立患者PFS和OS的列线图预测模型,采用受试者工作特征(receiver operating characteristics,ROC)曲线、校准曲线和临床决策曲线对模型进行评价。结果NOP2突变组与NOP2野生组患者的Child-Pugh分级、CNLC分期、肿瘤直径、肿瘤数目和门静脉侵犯的差异有统计学意义(P<0.05)。免疫治疗后NOP2突变组患者的ORR[60.71%(34/56)比31.68%(32/101)]和DCR[96.43%(54/56)比82.18%(83/101)]均显著高于NOP2野生组(P均<0.05)。NOP2突变组患者的PFS及OS均显著高于NOP2野生组(Log-Rankχ^(2)=3.822,P=0.033;Log-Rankχ^(2)=4.741,P=0.025)。多因素Cox回归分析表明,Child-Pugh B级(HR=2.120,95%CI:1.121~4.009,P=0.021;HR=2.411,95%CI:1.203~4.833,P=0.013)、CNLCⅣ期(HR=4.904,95%CI:2.070~11.617,P<0.001;HR=3.167,95%CI:1.472~6.810,P=0.003)、肿瘤直径≥61.72 mm(HR=3.065,95%CI:1.471~6.082,P<0.001;HR=2.967,95%CI:1.314~6.259,P<0.001)、肿瘤数目>3个(HR=3.374,95%CI:1.711~6.653,P<0.001;HR=2.358,95%CI:1.182~4.704,P=0.015)、门静脉侵犯(HR=3.176,95%CI:1.643~6.141,P=0.001;HR=3.173,95%CI:1.572~6.404,P<0.001)是肝�Objective To investigate the effects of NOP2 gene status on immunotherapy efficacy and prognosis of patients with liver cancer.Methods Total of 157 patients with liver cancer hospitalized in People’s Hospital of Dingzhou from June 2017 to June 2020 were selected as the study subjects.According to the status of NOP2 gene,the patients were divided into NOP2 mutation group(56 cases)and NOP2 wild group(101 cases).The clinical data[including gender,age,body mass index(BMI),China clinic liver cancer staging(CNLC staging),Child-Pugh score,Eastern Cooperative Oncology Group(ECOG),etc.],immunotherapy efficacy[objective response rate(ORR),disease control rate(DCR)]and prognosis of patients in two groups were compared.The patients were followed for 3 years,and their overall survival(OS)and progression-free survival(PFS)were recorded.Kaplan-Meier method was used to plot survival curves and analyze PFS and OS of liver cancer patients with different NOP2 gene states.Univariate and multivariate Cox regression analysis were used to analyze the influence factors affecting PFS and OS in patients with liver cancer.A monograms prediction model for PFS and OS was established,and receiver operating characteristics(ROC)curve,calibration curve,and clinical decision curve were used to evaluate the model.Results There were statistically significant differences between patients in NOP2 mutant group and NOP2 wild group in terms of Child-Pugh grading,CNLC staging,tumor diameter,number of tumors and portal vein invasion(all P<0.05).After immunotherapy,the ORR[60.71%(34/56)vs.31.68%(32/101)]and DCR[96.43%(54/56)vs.82.18%(83/101)]of patients in NOP2 mutant group were significantly higher than those of NOP2 wild group(all P<0.05).PFS and OS of patients in NOP2 mutation group were significantly higher than those of NOP2 wild group(Log-Rankχ^(2)=3.822,P=0.033;Log-Rankχ^(2)=4.741,P=0.025).Multivariate Cox regression analysis showed that Child-Pugh grade B(HR=2.120,95%CI:1.121~4.009,P=0.021;HR=2.411,95%CI:1.203~4.833,P=0.013),CNLC stagingⅣ(HR=

关 键 词：NOP2基因 免疫治疗 肝癌 

分 类 号：R73[医药卫生—肿瘤]