Shanghai Gemple Biotechnology Co Ltd.
Int J Gynecol Cancer. 2018 Nov;28(9):1812-1820. doi: 10.1097/IGC.0000000000001365.
High-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.
Fresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.
The total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.
The combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.
高危型子宫内膜癌（EC）包括高级别 EC、浆液性癌（SC）、透明细胞癌和癌肉瘤，占 EC 死亡病例的 50%。这些癌症的治疗方法有限，而患者来源的肿瘤异种移植（PDTX）模型是评估临床前药物、鉴定生物标志物和制定个体化医疗策略的有用工具。在此，我们使用并比较了两种方法来建立 PDTX 模型。
从 18 名高危 EC 患者（10 例高级别 EC、6 例 SC、1 例透明细胞癌和 1 例癌肉瘤）的新鲜肿瘤组织中，分别进行皮下和肾包膜下种植，以建立 NOD/SCID 模型，并在 Balb/c-nu/nu 小鼠中进行扩增。评估组织学和细胞角蛋白、雌激素受体、孕激素受体和 P53 表达，以评估原发肿瘤和不同代次 PDTX 肿瘤的相似性。对 2 例高级别 EC 模型进行全外显子组测序（WES）和 RNA 测序，以验证原发肿瘤和 PDTX 肿瘤之间的遗传突变谱和基因表达是否相似。
无论采用何种种植方法，总肿瘤种植率均为 77.8%（14/18）。与皮下模型相比，肾包膜下模型的肿瘤种植率增加（62.5%比 50%，P=0.464）。肿瘤形成时间从 2 周到 11 周不等。肾包膜下种植后，移植瘤可成功移植到皮下部位。我们观察到原发肿瘤与相应的异种移植不同代次之间具有良好的相似性。
两种种植方法的结合可提高肿瘤种植率。高肿瘤种植率确保了高危型 EC 生物样本库的建立，这是进行临床前药物敏感性测试和鉴定反应或耐药的生物标志物的有力资源。
