结直肠癌PDX模型成瘤率的影响因素及临床意义  

Influencing factors and the clinical significance of tumorigenesis rate in PDX model of colorectal cancer

作　　者：张燕萍 姚刘旭 丁倩男[2] 黄则勇 李玉红 黄素琴 ZHANG Yanping;YAO Liuxu;DING Qiannan;HUANG Zeyong;LI Yuhong;HUANG Suqin(Department of Anesthesiology,Shulan(Hangzhou)Hospital,Hangzhou 310004;Clinical Research Center,Shaoxing People's Hospital,Shaoxing 312000;Department of Anesthesiology,Shulan(Hangzhou)Hospital,Shulan International Medical College,Zhejiang Shuren College,Hangzhou 310004,China)

机构地区：[1]树兰(杭州)医院麻醉科,浙江杭州310004 [2]绍兴市人民医院医学研究中心,浙江绍兴312000 [3]浙江树人学院树兰国际医学院附属树兰(杭州)医院麻醉科,浙江杭州310004

出　　处：《基础医学与临床》2023年第4期596-602,共7页Basic and Clinical Medicine

基　　金：浙江省科学技术厅公益项目(LY21H150001);浙江省医药卫生科技计划项目(2020KY329);绍兴市科技项目(2020A13014);杭州市科技项目(B20210683)。

摘　　要：目的建立结直肠癌(CRC)患者来源的肿瘤组织异种移植(PDX)模型,评估PDX模型成瘤率的影响因素,并初步进行化学治疗实验。方法选取2019年11月至2020年10月绍兴市人民医院择期手术CRC患者。将手术获取的肿瘤组织接种于NSG小鼠右侧腰背部,建立PDX模型,并传至F3代,分析PDX模型成瘤率的影响因素;化学治疗药物选择5-氟尿嘧啶、奥沙利铂以及丙泊酚。结果本研究共纳入60例CRC患者,PDX模型成瘤为37例,成瘤率62%;平均成瘤时间为(34±12)d;原发瘤恶性程度(CRC分期和细胞分化程度)、术前癌胚抗原(CEA)水平以及肿瘤位置等因素影响PDX模型成瘤率(P<0.01)。CRC-PDX移植瘤组织与患者肿瘤组织生物学特征高度一致。4种化学治疗方案均能抑制肿瘤生长,致肿瘤组织破坏,丙泊酚可以抑制小鼠腹泻,对肠黏膜具有保护作用。结论本研究建立的CRC-PDX模型,较好地保持原发肿瘤的生物学特性,可作为CRC患者个体化治疗的参考模型。原发肿瘤恶性程度是PDX模型成瘤率的主要影响因素。Objective To establish a patient derived xenograft(PDX)model of tumor tissue from patients with colorectal cancer(CRC)and to identify the factors affecting the tumorigenesis rate of PDX model,as well as to conduct a preliminary chemotherapy.Methods From November 2019 to October 2020,CRC patients undergoing elective surgery in Shaoxing People s Hospital were selected.The tumor tissue obtained from surgical operation was inoculated to the right lumbar back of NSG mice to establish a PDX model,which was subcultured to F3 generation,and the influencing factors of the tumor formation rate of PDX model were analyzed.Chemotherapy drugs include 5-fluorouracil,oxaliplatin and anesthetic propofol.Results A total of 60 patients with CRC were included in this study and 37 samples from patients had PDX tumor formation in mice with a tumorigenesis rate of 62%;The average tumorigenesis time was(34±12)d;Primary tumor malignant degree(tumor stage and degree of cell differentiation),preoperative carcinoembryonic antigen(CEA)level and tumor location of CRC patients affected the tumorigenesis rate of PDX model(P<0.01).The biology of CRC-PDX transplanted tumor tissue was highly consistent with that of the patient s tumor tissue.All four chemotherapy regimens could inhibit tumor growth and cause tumor tissue damage.Propofol could inhibit diarrhea in mice and protect intestinal mucosa.Conclusions The CRC-PDX model established in this study may better keep biological characteristics of primary tumors and be used as a reference model for individualized treatment of CRC patients.The malignant degree of the primary tumor is the main factor affecting the tumorigenesis rate of PDX model.

关 键 词：结直肠癌 患者来源异种移植 影响因素 成瘤率 个体化治疗 

分 类 号：R73[医药卫生—肿瘤]