Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression

被引:731
作者
Rhodes, DR
Yu, JJ
Shanker, K
Deshpande, N
Varambally, R
Ghosh, D
Barrette, T
Pandey, A
Chinnaiyan, AM [1 ]
机构
[1] Inst Bioinformat, Bangalore 560066, Karnataka, India
[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Sch Med, Dept Bioinformat, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA
[8] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
关键词
D O I
10.1073/pnas.0401994101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Many studies have used DNA microarrays to identify the gene expression signatures of human cancer, yet the critical features of these often unmanageably large signatures remain elusive. To address this, we developed a statistical method, comparative metaprofiling, which identifies and assesses the intersection of multiple gene expression signatures from a diverse collection of microarray data sets. We collected and analyzed 40 published cancer microarray data sets, comprising 38 million gene expression measurements from >3,700 cancer samples. From this, we characterized a common transcriptional profile that is universally activated in most cancer types relative to the normal tissues from which they arose, likely reflecting essential transcriptional features of neoplastic transformation. In addition, we characterized a transcriptional profile that is commonly activated in various types of undifferentiated cancer, suggesting common molecular mechanisms by which cancer cells progress and avoid differentiation. Finally, we validated these transcriptional profiles on independent data sets.
引用
收藏
页码:9309 / 9314
页数:6
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