胰腺癌类器官模型的构建与应用  

Construction and application of patient-derived pancreatic tumor organoid model

作　　者：李鹏[1,2] 黄敏丽 谭邓旭 张彩勤 张永斌[1] 师长宏[2] LI Peng;HUANG Minli;TAN Dengxu;ZHANG Caiqin;ZHANG Yongbin;SHI Changhong(Animal Laboratory Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Laboratory Animal Center,the Fourth Military Medical University,Xi’an 710032)

机构地区：[1]广州中医药大学动物实验中心,广州510405 [2]第四军医大学实验动物中心,西安710032

出　　处：《中国比较医学杂志》2024年第6期40-46,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(32270566)。

摘　　要：目的 构建胰腺癌类器官(patient-derived tumor organoid, PDO)并进行药物治疗评价,评估PDO模型的有效性。方法 收集胰腺癌患者新鲜手术标本,用于PDO培养;分析PDO模型与原发瘤的病理学和遗传学特征;利用PDO模型开展临床化疗药物的疗效评价,测试模型的有效性。结果 成功建立一例胰腺癌PDO模型,组织形态学分析显示PDO模型基本保持了原发肿瘤病理学特征。全外显子测序结果显示,PDO在基因突变类型和特征方面与原始肿瘤保持一致。药物筛选试验显示,PDO模型对临床常用的化疗药物吉西他滨、伊立替康具有较好的敏感性。结论 成功构建了一例胰腺癌PDO模型,该模型能够反应原始肿瘤的组织学和遗传学特征,并可以进行体外药物敏感性实验,证明了PDO模型的有效性,有望应用于胰腺癌的个体化治疗。Objective To construct a patient-derived pancreatic tumor organoid(PDO)and evaluate its effectiveness.Methods We collected fresh surgical specimens from pancreatic cancer patients for PDO culture and compared the pathological and genetic characteristics of the PDO model with those of primary tumors.The PDO model was used to evaluate the efficacy of clinical chemotherapy drugs,and the effectiveness of the model was assessed.Results A PDO model of pancreatic cancer was successfully established.Histomorphological analysis indicated that the PDO model maintained the basic pathological characteristics of the primary tumor.Whole-exon sequencing showed that both the organoids and original tumor tissue remained consistent in their gene mutation type and characteristics.Drug screening tests revealed that the PDO model had good sensitivity to gemcitabine and irinotecan.Conclusions A pancreatic cancer PDO was successfully constructed that reflected the histological and genetic characteristics of the original tumor.The model was shown to be effective for drug sensitivity experiments in vitro and is expected to have implications for precision medicine assays.

关 键 词：胰腺癌 类器官 药物筛选 个体化治疗 

分 类 号：R-33[医药卫生]