Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers
Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers
复制标题
DOI：
10.1158/0008-5472.can-06-3322
复制
发表时间：
2007-04-01
期刊：
影响因子：
11.2
通讯作者：
Harris, Adrian L.
中科院分区：
文献类型：
--
作者：
Winter, Stuart C.;Buffa, Francesca M.;Harris, Adrian L.
使用Affytron U133 plus 2基因芯片分析了59例头颈部鳞状细胞癌。通过分析其体内表达与10种众所周知的低氧调节基因（例如，CA 9、GLUT 1和VEGF）。为了使随机聚集最小化，出现在> 50%的簇中的强相关上调基因定义了包含99个基因的标记，其中27%先前已知是缺氧相关的。在公开的头颈癌数据集中，签名中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。在已发表的乳腺癌系列研究中，缺氧标志物是总生存期的重要预后因素，与临床病理学风险因素和训练特征无关。这项工作突出了使用来自体外应激途径分析的数据在体内获得生物元基因/基因签名的有效性和潜力。
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.