Gene expression analysis reveals close resemblance between Glioblastoma (GBM) patient tumors and corresponding patient-derived orthotopic xenografts (PDOXs)

Glioblastoma (GBM) patient-derived orthotopic xenografts (PDOXs) were derived from organotypic spheroids obtained from patient tumor samples. To detect whether gene expression profiles of GBM patient tumors are retained in PDOXs, we performed genome-wide transcript analysis by human-specific microarrays . In parallel, we analyzed GBM cell cultures and corresponding intracranial xenografts from stem-like (NCH421k, NCH644) and adherent GBM cell lines (U87, U251). PDOXs show a better transcriptomic resemblance with patient tumors than other preclinical models. The major difference is largely explained by the depletion of human-derived non-malignant cells. 58 samples from human GBM patient tumor samples (n=6), GBM PDOXs (6 PDOX models, n=1-3), GBM cell lines (5 cell lines, n= 3-6 per line), GBM cell line-derived xenografts (5 cell lines, n= 2-4 per line) and human normal brain RNA (n=2) were analysed using GeneChip® Human Gene 1.0ST affymetrix array.

胶质母细胞瘤（Glioblastoma, GBM）患者来源的原位异种移植瘤（patient-derived orthotopic xenografts, PDOXs）源自从患者肿瘤样本中获取的器官型球状体。为验证GBM患者肿瘤的基因表达谱是否可在PDOX中得以保留，我们采用人源特异性微阵列开展了全转录组分析。与此同时，我们还分析了干细胞样（NCH421k、NCH644）及贴壁型GBM细胞系（U87、U251）来源的GBM细胞培养物与对应颅内异种移植瘤。相较于其他临床前模型，PDOX与患者肿瘤的转录组相似性更优，二者的核心差异在很大程度上可归因于人源非恶性细胞的耗竭。本研究采用Affymetrix GeneChip® Human Gene 1.0ST基因芯片，对58份样本开展了转录组分析，样本涵盖：人GBM患者肿瘤样本（n=6）、GBM PDOX样本（6种PDOX模型，n=1~3/模型）、GBM细胞系样本（5株细胞系，n=3~6/株）、细胞系来源的GBM异种移植瘤样本（5株细胞系，n=2~4/株）以及人正常脑组织RNA样本（n=2）。