Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cells. 2019 Jul 11;8(7):702. doi: 10.3390/cells8070702.
Accurate patient-derived models of cancer are needed for profiling the disease and for testing therapeutics. These models must not only be accurate, but also suitable for high-throughput screening and analysis. Here we compare two derivative cancer models, microtumors and spheroids, to the gold standard model of patient-derived orthotopic xenografts (PDX) in (GBM). To compare these models, we constructed a custom NanoString panel of 350 genes relevant to GBM biology. This custom assay includes 16 GBM-specific gene signatures including a novel GBM subtyping signature. We profiled 11 GBM-PDX with matched orthotopic cells, derived microtumors, and derived spheroids using the custom NanoString assay. In parallel, these derivative models underwent drug sensitivity screening. We found that expression of certain genes were dependent on the cancer model while others were model-independent. These model-independent genes can be used in profiling tumor-specific biology and in gauging therapeutic response. It remains to be seen whether or not cancer model-specific genes may be directly or indirectly, through changes to tumor microenvironment, manipulated to improve the concordance of in vitro derivative models with in vivo models yielding better prediction of therapeutic response.
为了对疾病进行分析并测试治疗方法，需要有精确的、源自患者的癌症模型。这些模型不仅必须准确，而且还必须适合高通量筛选和分析。在这里，我们将两种衍生的癌症模型（微肿瘤和球体）与源自患者的原位异种移植（PDX）的金标准模型（GBM）进行了比较。为了比较这些模型，我们构建了一个包含 350 个与 GBM 生物学相关的基因的定制 NanoString 面板。该定制检测包括 16 个 GBM 特异性基因特征，包括一个新的 GBM 亚型特征。我们使用定制的 NanoString 检测方法对 11 个 GBM-PDX 及其匹配的原位细胞、衍生的微肿瘤和衍生的球体进行了分析。同时，这些衍生模型还进行了药物敏感性筛选。我们发现，某些基因的表达取决于癌症模型，而其他基因则与模型无关。这些与模型无关的基因可用于分析肿瘤特异性生物学，并评估治疗反应。目前尚不清楚癌症模型特异性基因是否可以直接或间接地通过改变肿瘤微环境来操纵，以提高体外衍生模型与体内模型的一致性，从而更好地预测治疗反应。
