人源性胰腺肿瘤异种移植模型建立与临床意义

Xenotransplantation model of human pancreatic tumor and its clinical significance

目的评估影响建立胰腺癌人源性肿瘤异种移植(PDX)模型的临床病理因素,并初步进行药敏实验。方法选取2018年1-12月在海军军医大学附属长海医院胰腺肝胆外科就诊的胰腺导管腺癌患者,将手术获取的肿瘤组织移植至NSG小鼠(NOD-SCID)侧腹部皮下,建立PDX模型。单变量和多变量分析寻找可影响PDX成瘤的临床和病理因素。评估移植肿瘤生长速度与原发肿瘤的相关性,并进行组织学比较。药敏实验方案包括吉西他滨、替吉奥、丝裂霉素、GS方案、FOLFIRINOX方案和GP方案等。结果本研究共纳入101例胰腺导管腺癌患者,PDX模型建立成功74例,成功率73.3%(74/101);74例PDX模型平均成瘤时间(100.5±44.8)d。在多变量分析中,T分期是唯一可影响PDX模型建立成功与否的独立危险因素(P=0.030)。PDX生长与原发肿瘤大小存在相关性,并能较好的保持原发肿瘤的病理形态特征。36例PDX模型的药敏结果为:吉西他滨10例,替吉奥11例,丝裂霉素3例,GS方案14例,FOLFIRINOX方案14例和GP方案16例。结论胰腺癌PDX模型成瘤率高,并较好保持了原发肿瘤的生物学特性和病理特征,可作为胰腺癌个体化治疗的参考模型。

Objective To evaluate the clinicopathological factors influencing the establishment of patient derived xenograft(PDX)model for pancreatic cancer,and to conduct a preliminary drug sensitivity test.Methods PDX model was established by transplantation of tumor tissues obtained from surgery into the lateral abdominal subcutaneous of NSG mice(NOD-SCID),selected from pancreatic duct adenocarcinoma patients who were admitted from January to December of 2018.Univariate and multivariate analyses were conducted to identify clinical and pathological factors that may affect PDX tumorigenesis.The correlation between the growth rate of transplanted tumor and the primary tumor was evaluated and compared histologically.Drug sensitivity test regimens include gemcitabine,S-1,mitomycin,GS regimens,FOLFIRINOX regimens and GP regimens.Results A total of 101 patients with pancreatic ductal adenocarcinoma were included in this study,and 74 of them succeeded in establishing the PDX model,with a success rate of 73.3%(74/101).The mean tumorigenic time of 74 PDX models were(100.5±44.8)days.In multivariate analysis,T staging was the only independent risk factor that can affect the success of PDX model establishment(P=0.030).The growth of PDX was correlated with the size of primary tumor and can maintain the pathological morphological characteristics of primary tumor.The results of drug sensitivity of 36 PDX models were as follows:10 cases of gemcitabine,11 cases of S-1,3 cases of mitomycin,14 cases of GS regimen,14 cases of FOLFIRINOX regimen and 16 cases of GP regimen.Conclusion The PDX model of pancreatic cancer has a high rate of tumor formation and maintains the biological and pathological characteristics of the primary tumor,which can be used as a reference model for individualized treatment of pancreatic cancer.