Winter Stuart C, Buffa Francesca M, Silva Priyamal, Miller Crispin, Valentine Helen R, Turley Helen, Shah Ketan A, Cox Graham J, Corbridge Rogan J, Homer Jarrod J, Musgrove Brian, Slevin Nick, Sloan Philip, Price Pat, West Catharine M L, Harris Adrian L
Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital.
Cancer Res. 2007 Apr 1;67(7):3441-9. doi: 10.1158/0008-5472.CAN-06-3322.
Affymetrix U133plus2 GeneChips were used to profile 59 head and neck squamous cell cancers. A hypoxia metagene was obtained by analysis of genes whose in vivo expression clustered with the expression of 10 well-known hypoxia-regulated genes (e.g., CA9, GLUT1, and VEGF). To minimize random aggregation, strongly correlated up-regulated genes appearing in >50% of clusters defined a signature comprising 99 genes, of which 27% were previously known to be hypoxia associated. The median RNA expression of the 99 genes in the signature was an independent prognostic factor for recurrence-free survival in a publicly available head and neck cancer data set, outdoing the original intrinsic classifier. In a published breast cancer series, the hypoxia signature was a significant prognostic factor for overall survival independent of clinicopathologic risk factors and a trained profile. The work highlights the validity and potential of using data from analysis of in vitro stress pathways for deriving a biological metagene/gene signature in vivo.
使用Affymetrix U133plus2基因芯片对59例头颈部鳞状细胞癌进行基因表达谱分析。通过分析体内表达与10个著名的缺氧调节基因（如CA9、GLUT1和VEGF）的表达聚类的基因，获得了一个缺氧元基因。为了尽量减少随机聚集，在超过50%的聚类中出现的强相关上调基因定义了一个由99个基因组成的特征，其中27%以前已知与缺氧相关。在一个公开的头颈部癌数据集中，该特征中99个基因的中位RNA表达是无复发生存的独立预后因素，优于原始的内在分类器。在一个已发表的乳腺癌系列中，缺氧特征是总生存的一个重要预后因素，独立于临床病理危险因素和一个经过训练的特征。这项工作突出了利用体外应激途径分析数据在体内推导生物学元基因/基因特征的有效性和潜力。
