Pancreatic cancer has one of the worst prognoses among all malignancies and few available treatment options. Patient-derived xenografts can be used to develop personalized therapy for pancreatic cancer. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) may provide a powerful alternative to surgery for obtaining sufficient tissue for the establishment of patient-derived xenografts. In this study, EUS-FNA samples were obtained for 30 patients referred to the Ottawa Hospital, Ottawa, Ontario, Canada. These samples were used for xenotransplantation in NOD-SCID mice and for genetic analyses. The gene expression of pancreatic-cancer-relevant genes in xenograft tumors was examined by immunohistochemistry. Targeted sequencing of both the patient-derived tumors and xenograft tumors was performed. The xenografts’ susceptibility to oncolytic virus infection was studied by infecting xenograft-derived cells with VSV∆51-GFP. The xenograft take rate was found to be 75.9% for passage 1 and 100% for passage 2. Eighty percent of patient tumor samples were successfully sequenced to a high depth for 42 cancer genes. Xenograft histological characteristics and marker expression were maintained between passages. All tested xenograft samples were susceptible to oncoviral infection. We found that EUS-FNA is an accessible, minimally invasive technique that can be used to acquire adequate pancreatic cancer tissue for the generation of patient-derived xenografts and for genetic sequencing.
胰腺癌在所有恶性肿瘤中预后最差，且治疗选择有限。患者来源的异种移植模型可用于开发胰腺癌的个体化治疗方案。内镜超声引导下细针穿刺活检（EUS-FNA）可能成为手术之外获取足够组织建立患者来源异种移植模型的有效替代方法。本研究对加拿大安大略省渥太华医院收治的30例患者进行了EUS-FNA取样，将获取的样本用于NOD-SCID小鼠异种移植及基因分析。通过免疫组化检测了异种移植瘤中胰腺癌相关基因的表达情况，并对患者来源肿瘤及异种移植瘤进行了靶向测序。通过VSV∆51-GFP病毒感染异种移植来源细胞，研究了移植瘤对溶瘤病毒感染的敏感性。结果显示：第一代移植成功率为75.9%，第二代达100%；80%的患者肿瘤样本成功完成42个癌症基因的高深度测序；异种移植瘤的组织学特征和标志物表达在传代过程中保持稳定；所有测试的异种移植样本均对溶瘤病毒感染敏感。研究表明，EUS-FNA作为一种可及性高、微创的技术，能够获取足够的胰腺癌组织用于建立患者来源异种移植模型并进行基因测序。
肿瘤(癌症)患者之家