肝细胞癌患者免疫功能和炎症因子水平与体外高通量药物敏感度的相关性研究  

Correlation study of immune function and inflammatory factors levels in patients with hepatocellular carcinoma and in vitro high-throughput drug sensitivity

作　　者：冯国英 陈凯[1] 杨旭[1] 陶杰 史政荣[1] FENG Guoying;CHEN Kai;YANG Xu;TAO Jie;SHI Zhengrong(Department of Hepatobiliary Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,P.R.China)

机构地区：[1]重庆医科大学附属第一医院肝胆外科,重庆400016

出　　处：《中国普外基础与临床杂志》2022年第6期748-755,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：2019年重庆市科卫联合医学科研计划项目中青年高端人才项目(项目编号:2019GDRC002)。

摘　　要：目的分析肝细胞癌(简称“肝癌”)患者免疫功能和炎症因子水平与体外高通量药物敏感度试验结果的相关性,为肝癌患者个性化药物选择提供参考。方法纳入重庆医科大学附属第一医院2019年12月至2021年6月期间符合纳入标准的肝癌患者,使用肝癌细胞进行体外高通量药物敏感度试验,结果分为敏感与不敏感,分析药物敏感度与对应患者的免疫功能和炎症因子水平指标的相关性,并进一步对具有相关性(P<0.05)的指标采用单因素logistic回归分析这些指标与肝癌细胞对药物敏感度的关系。结果本研究共纳入74例肝癌患者,结果发现,白细胞介素-6(interleukin-6,IL-6)水平与索拉非尼、卡非佐米、吉西他滨及联合方案奥沙利铂+表柔比星+伊立替康+5-氟尿嘧啶方案、奥沙利铂+伊立替康+表柔比星方案和奥沙利铂+表柔比星方案对肝癌细胞的体外抑制率呈负相关关系(P<0.05),与硼替佐米对肝癌细胞的体外抑制率呈正相关关系(P<0.05),但未发现IL-6水平与这些单药或联合方案用药对肝癌细胞的敏感度有关(P>0.05);还发现,肿瘤坏死因子-α水平与卡博替尼、阿帕替尼、卡非佐米和表柔比星对肝癌细胞的体外抑制率呈负相关关系(P<0.05),与多柔比星对肝癌细胞的体外抑制率呈正相关关系(P<0.05),但仅发现肿瘤坏死因子-α水平与表柔比星对肝癌细胞的敏感度有关(P<0.05)。结论肝癌患者外周血中肿瘤坏死因子-α水平与表柔比星对肝癌细胞的体外抑制率有一定的关系且其在肝癌细胞对表柔比星的敏感度预测中有一定的价值,同时虽然发现IL-6水平与硼替佐米、索拉非尼、卡非佐米、吉西他滨以及包含奥沙利铂和表柔比星的3种联合方案对肝癌细胞的体外抑制率有一定的关系,但未发现其在预测肝癌细胞对这些药物或方案的敏感度方面的价值。Objective To analyze the correlations between the immune function and inflammatory factors levels of patients with hepatocellular carcinoma(HCC)and the results of in vitro high-throughput drug sensitivity,and to provide a reference for personalized drug selection for patients with HCC.Methods The patients with HCC who met the inclusion criteria from December 2019 to June 2021 in the First Affiliated Hospital of Chongqing Medical University were included.The HCC cells were used to perform in vitro high-throughput drug sensitivity screening,the result was classified into sensitive and insensitive.The correlations between drug sensitivity results and immune function and inflammatory factors levels of corresponding patients were analyzed,and the relation between these indexes(P<0.05)and drug sensitivity of HCC cells to drugs or combination regimen of drugs was further analyzed by univariate logistic regression.Results A total of 74 patients with HCC were included in this study.The results showed that the level of interleukin-6was negatively correlated with sorafenib,caffezomib,gemcitabine,oxaliplatin+epirubicin+irinotecan+5-fluorouracil,oxaliplatin+irinotecan+epirubicin,and oxaliplatin+epirubicin regimens on the inhibition rates of HCC in vitro(P<0.05),and positively correlated with bortezomib(P<0.05).However,the level of interleukin-6 was not related to the sensitivity of HCC cells to these single drugs or combined regimens(P>0.05).Meanwhile it was found that tumor necrosis factor(TNF)-αwas negatively correlated with cabotinib,apatinib,caffezomib,and epirubicin on the inhibition rates of HCC in vitro(P<0.05),and positively correlated with epirubicin(P<0.05).But only it was found that tumor necrosis factor-αlevel was related to the sensitivity of HCC cells to epirubicin(P<0.05).Conclusions Tumor necrosis factor-αlevel in peripheral blood of patients with HCC has a certain relation with epirubicin on inhibition rate of HCC in vitro and it might have a certain value in predicting sensitivity of HCC cells to epirubic

关 键 词：肝细胞癌 体外高通量药物敏感度筛选 免疫功能 炎症因子 

分 类 号：R735.7[医药卫生—肿瘤]