胰腺癌类器官模型的构建与应用
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1.广州中医药大学动物实验中心;2.第四军医大学实验动物中心

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国家自然科学基金项目(面上项目,重点项目,重大项目)


Construction and application of patient-derived pancreatic tumor organoid model
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Affiliation:

1.Animal Laboratory Center,Guangzhou University of Chinese Medicine;2.Laboratory Animal Center, The Fourth Military Medical University

Fund Project:

The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

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    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。

    Abstract:

    Objective To construct a patient-derived pancreatic tumor organoid (PDO) and evaluate its effectiveness. Methods Collect fresh surgical specimens from pancreatic cancer patients for PDO culture; Compared the pathological and genetic characteristics of the PDO model with the primary tumors; Using the PDO model to evaluate the efficacy of clinical chemotherapy drugs and evaluate the effectiveness of the model. Results A PDO model of pancreatic cancer was successfully established. Histomorphological analysis displayed that the PDO model basically maintained the pathological characteristics of the primary tumor. Whole-exon sequencing showed that both organoids and original tumor tissue remained consistent in the gene mutation type and characteristics. Drug screening tests have exhibited that the PDO model had good sensitivity to gemcitabine and irinotecan. Conclusion A case of pancreatic cancer PDO was successfully constructed, which can reflect the histological and genetic characteristics of the original tumor, and can be used for drug sensitivity experiments in vitro, which proves the effectiveness of PDO model and is expected to imply precision medicine.

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  • 收稿日期:2023-11-10
  • 最后修改日期:2023-12-28
  • 录用日期:2024-03-20
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