Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, Maastricht University, The Netherlands.
Radiother Oncol. 2009 Sep;92(3):417-22. doi: 10.1016/j.radonc.2009.06.016. Epub 2009 Jul 15.
To investigate the use of xenograft models in a novel gene signature validation method using gene expression microarrays.
Gene expression profiles of ten human Head and Neck squamous cell carcinomas (HNSCCs) were obtained. Several published prognostic gene expression signatures were evaluated within this set. These consisted of different radiotherapy relevant signatures (i.e. for hypoxia, proliferation and 'stemness'). Signatures were correlated with various endpoints that have been determined in the ten different xenograft models. These include immunohistochemical measures for hypoxia and proliferation, volume doubling time (VDT) and local tumour control after fractionated irradiation or after single dose irradiation under clamp hypoxia.
We found several significant correlations between the published gene expression signatures and tumour parameters. Several signatures, like the proliferation and wound signature correlated with BrdU labelling index. Further a 'stemness'-related gene signature showed a strong negative correlation with hypoxic fraction.
Simultaneous assessment of immunohistochemistry, in vivo tumour properties and gene expression profiling in a comprehensive set of xenograft models can be used to validate and potentially infer biological information about prognostic gene signatures.
研究异种移植模型在使用基因表达微阵列的新型基因特征验证方法中的应用。
获得了十个人类头颈部鳞状细胞癌（HNSCC）的基因表达谱。在此组内评估了几个已发表的与预后相关的基因表达特征。这些特征包括与各种终点相关的不同放射治疗相关特征（例如缺氧、增殖和“干性”）。特征与在十个不同异种移植模型中确定的各种终点相关联。这些终点包括缺氧和增殖的免疫组织化学测量、倍增时间（VDT）以及分割照射后的局部肿瘤控制或夹闭缺氧下的单次照射后。
我们发现已发表的基因表达特征与肿瘤参数之间存在几个显著相关性。几个特征，如增殖和伤口特征与 BrdU 标记指数相关。此外，与“干性”相关的基因特征与缺氧分数呈强负相关。
在综合的异种移植模型中同时评估免疫组织化学、体内肿瘤特性和基因表达谱可用于验证和潜在推断预后基因特征的生物学信息。
