Abstract:
Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.
摘要:
胰腺神经内分泌肿瘤是胰腺第二常见的肿瘤,大约一半的患者被诊断为肝转移。目前,相关治疗方法的疗效改善仍然有限。因此,目前迫切需要对胰腺神经内分泌肿瘤的分子生物学机制进行深入研究。然而,由于它们相对惰性的生物学,临床前模型极其稀缺。这里,患者来源的类器官,并成功构建了患者来源的异种移植物。这两个模型和先前构建的名为SPNE1的细胞系都来自患有3级非功能性胰腺神经内分泌肿瘤的同一患者,提供新的肿瘤建模平台,并使用免疫组织化学进行表征,全外显子组测序,和单细胞转录组测序。结合免疫缺陷小鼠的肿瘤形成实验,我们选择了最接近概括亲本肿瘤的模型.总的来说,患者来源的异种移植模型最类似于人类肿瘤组织.