患者源性类器官作为评估胰腺癌治疗反应预测模型的临床研究  

Clinical study on patient-derived organoids as a predictive model for assessing treatment response in pancreatic cancer

作　　者：沈素雅 李晶晶 程浩[1] 管文燕[1] 李志文[1] 伏晓[1] 胡颖哲 蔡正华 韩宇庆 仇毓东[1] Shen Suya;Li Jingjing;Cheng Hao;Guan Wenyan;Li Zhiwen;Fu Xiao;Hu Yingzhe;Cai Zhenghua;Han Yuqing;Qiu Yudong(Department of Pancreatic Surgery,Nanjing Drum Tower Hospital,Nanjing University,Medical School,Nanjing,210008 China;Center for Precision Medicine,Nanjing Drum Tower Hospital,Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院胰腺外科,南京210008 [2]南京大学医学院附属鼓楼医院精准医学中心,南京210008

出　　处：《中华普通外科杂志》2023年第9期655-661,共7页Chinese Journal of General Surgery

基　　金：国家自然科学基金(31971518)。

摘　　要：目的通过构建胰腺癌患者源性肿瘤类器官(patient derived organoids,PDOs)生物样本库,探索PDOs药敏检测技术指导胰腺癌化疗药物选择的可行性。方法收集2020年3月至2022年12月在南京大学医学院附属鼓楼医院接受手术切除和穿刺活检患者的胰腺癌组织标本,体外培养胰腺癌PDOs并进行组织学鉴定;采用吉西他滨(Gemcitabine)、白蛋白结合型紫杉醇(nab-Paclitaxel)、氟尿嘧啶(5-Fluorouracil)、奥沙利铂(Oxaliplatin)、伊利替康(Irinotecan)处理PDOs并进行细胞活力测定,分析PDOs药物敏感性与患者实际临床治疗反应的相关性。结果PDOs可再现原肿瘤组织的病理学特征;不同PDOs对同一化疗药物的敏感性具有显著差异;PDOs药物敏感性与患者实际治疗效果的一致性为75.76%(25/33);基于类器官的药敏检测对患者治疗反应具有预测价值(AUC=0.733,95%CI:0.546~0.919,P<0.05)。结论本研究成功构建胰腺癌PDOs生物样本库,其药敏检测结果与患者实际用药反应具有显著相关性,基于PDOs的药敏检测技术具有指导胰腺癌个体化治疗的潜力。Objective To construct a biospecimen bank of patient derived organoids(PDOs)from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital,Nanjing University School of Medicine were collected.Pancreatic cancer PDOs were cultured in vitro and histologically identified;PDOs were treated with gemcitabine,Nab-paclitaxel,fluorouracil,Oxaliplatin,and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results The PDOs can reproduce the pathological features of corresponding tumor tissues;the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different;The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76%(25/33);organoid organ-based susceptibility testing had predictive value for the treatment response of patients(AUC=0.733,95%CI:0.546-0.919,P<0.05).Conclusion A biobank of pancreatic cancer PDOs was successfully constructed,and the drug susceptibility test results were significantly correlated with the actual medication response of patients,suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

关 键 词：胰腺肿瘤 类器官 辅助治疗 预后 

分 类 号：R735.9[医药卫生—肿瘤]