胰腺癌患者临床特征与异种移植模型的相关性

Correlation of Pancreatic Carcinoma Patients' Clinical Features and PDX Models

目的探索胰腺癌临床标本异种移植(PDX)模型成模率的影响因素,提高临床样本的利用率。方法采用裸鼠皮下移植的方法,建立稳定传代的胰腺癌PDX模型;综合分析62例胰腺癌患者的临床信息和肿瘤病理学特征对成模率的影响;通过STR基因分型检测、组织病理学特征及免疫组化检测P1代至P5代移植瘤和原发瘤的一致性。结果成功建立29例胰腺癌PDX模型,并稳定传代至P5代,模型总体成功率为47%;患者年龄、性别、患病史等临床信息与模型成功率无显著相关性(P>0.05);肿瘤的大小与模型成功率显著相关(P<0.05),淋巴浸润情况与成模率相关性极其显著(P<0.01),而肿瘤分化程度等其他病理学特征与成模率无相关性(P>0.05);P1代至P5代移植瘤在STR分型检测、组织病理学和特异性抗原CA19-9表达方面与原发瘤保持了较好的一致性。结论成功建立了29例胰腺癌PDX模型,与原发瘤保持了较好的相关性;移植瘤的大小及淋巴浸润情况是影响胰腺癌PDX模型成模的关键因素。

Objective To explore the influence factors of pancreatic carcinoma patient-derived xenograft（PDX）model and improve the utilization rate of clinical samples. Method Sixty-two patients＇ fresh pancreatic carcinoma specimens were transplanted subcutaneously into nude mice to establish PDX models. Correlation of the patients＇ clinical feature and PDX models were analysed in order to figure out the efficiency of modelling. The hereditary consistency of the primary tumors and xenograft tumor was detected by STR genotyping,and the similarity of tumor tissue structure were analysed by histopathological features and immunohistochemical examination. Result Total29 cases PDX models were established stabely,and total success rate reached to 47%（29/62）. The patients＇ clinical features did not show apparent correlation with the success rate of PDX models（P〈0. 05）. There were more significant correlation between primary tumors＇ size and PDX models（P〈0. 05）,especially for lymphatic metastasis（P〈0. 01）. The stabe consistency of primary tumors and transplanted tumors was confirmed by STR genotyping,histopathological features and CA19-9 expression. Conclusion We have successfully established 29 casespancreatic carcinoma PDX model. Primary tumors ＇ size and lymphatic metastasis were the key influence factors on success rate of PDX models.