Home LiteratureArticle Details
PMID: 15184677 Published · ppublish English Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 25 ·2004-06-22 ·Pages 9309-14

Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM

Abstract

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.

MeSH Terms
Cell Transformation, Neoplastic/genetics Disease Progression Gene Expression Profiling Humans Neoplasms/genetics,pathology Oligonucleotide Array Sequence Analysis Transcription, Genetic/genetics
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rhodes Daniel R
Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.
Yu Jianjun
Shanker K
Deshpande Nandan
Varambally Radhika
Ghosh Debashis
Barrette Terrence
Pandey Akhilesh
Chinnaiyan Arul M
References (49)
49 references, click to expand
  1. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease.
    Cancer Res. 2002 Aug 1;62(15):4499-506 PMID: 12154061
  2. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning.
    Nat Med. 2002 Jan;8(1):68-74 PMID: 11786909
  3. Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas.
    Cancer Res. 2002 Aug 15;62(16):4722-9 PMID: 12183431
  4. Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma.
    Am J Pathol. 2002 Oct;161(4):1315-23 PMID: 12368205
  5. The polycomb group protein EZH2 is involved in progression of prostate cancer.
    Nature. 2002 Oct 10;419(6907):624-9 PMID: 12374981
  6. Proteasome inhibitors as new anticancer drugs.
    Curr Opin Oncol. 2002 Nov;14(6):628-34 PMID: 12409653
  7. Role of histone H3 lysine 27 methylation in Polycomb-group silencing.
    Science. 2002 Nov 1;298(5595):1039-43 PMID: 12351676
  8. A molecular signature of metastasis in primary solid tumors.
    Nat Genet. 2003 Jan;33(1):49-54 PMID: 12469122
  9. Gene expression analysis of prostate cancers.
    Mol Carcinog. 2002 Jan;33(1):25-35 PMID: 11807955
  10. Gene expression profiling predicts clinical outcome of breast cancer.
    Nature. 2002 Jan 31;415(6871):530-6 PMID: 11823860
  11. Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas.
    Cancer Res. 2002 Apr 1;62(7):2085-91 PMID: 11929829
  12. Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer.
    Breast Cancer Res. 2002;4(3):R3 PMID: 12052255
  13. Gene expression patterns in human liver cancers.
    Mol Biol Cell. 2002 Jun;13(6):1929-39 PMID: 12058060
  14. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma.
    N Engl J Med. 2002 Jun 20;346(25):1937-47 PMID: 12075054
  15. Gene expression correlates of clinical prostate cancer behavior.
    Cancer Cell. 2002 Mar;1(2):203-9 PMID: 12086878
  16. Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer.
    Cancer Res. 2002 Aug 1;62(15):4427-33 PMID: 12154050
  17. Identifying distinct classes of bladder carcinoma using microarrays.
    Nat Genet. 2003 Jan;33(1):90-6 PMID: 12469123
  18. Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis.
    Am J Pathol. 2003 Feb;162(2):521-31 PMID: 12547710
  19. Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray.
    Am J Pathol. 2003 Mar;162(3):925-32 PMID: 12598325
  20. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin.
    Cell. 2003 Mar 7;112(5):725-36 PMID: 12628191
  21. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays.
    Am J Pathol. 2003 Apr;162(4):1151-62 PMID: 12651607
  22. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning.
    Nat Med. 2003 Apr;9(4):416-23 PMID: 12640447
  23. Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling.
    Cancer Res. 2003 Apr 15;63(8):1865-70 PMID: 12702575
  24. Gene expression in lung adenocarcinomas of smokers and nonsmokers.
    Am J Respir Cell Mol Biol. 2003 Aug;29(2):157-62 PMID: 12600827
  25. Statistical significance for genomewide studies.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5 PMID: 12883005
  26. Comparative analyses of multi-species sequences from targeted genomic regions.
    Nature. 2003 Aug 14;424(6950):788-93 PMID: 12917688
  27. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11606-11 PMID: 14500907
  28. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
    EMBO J. 2003 Oct 15;22(20):5323-35 PMID: 14532106
  29. Gene expression patterns in ovarian carcinomas.
    Mol Biol Cell. 2003 Nov;14(11):4376-86 PMID: 12960427
  30. Clinical applications of anticancer drugs targeted to topoisomerase II.
    Biochim Biophys Acta. 1998 Oct 1;1400(1-3):173-84 PMID: 9748560
  31. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  32. Control of apoptosis and mitotic spindle checkpoint by survivin.
    Nature. 1998 Dec 10;396(6711):580-4 PMID: 9859993
  33. Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6745-50 PMID: 10359783
  34. Expression of Melk, a new protein kinase, during early mouse development.
    Dev Dyn. 1999 Aug;215(4):344-51 PMID: 10417823
  35. Comparative genomics of the eukaryotes.
    Science. 2000 Mar 24;287(5461):2204-15 PMID: 10731134
  36. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  37. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer.
    Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1176-81 PMID: 11158614
  38. Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays.
    Cancer Res. 2001 Apr 1;61(7):3124-30 PMID: 11306497
  39. Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling.
    Cancer Res. 2001 Jun 15;61(12):4683-8 PMID: 11406537
  40. Expression profiling reveals hepsin overexpression in prostate cancer.
    Cancer Res. 2001 Aug 1;61(15):5692-6 PMID: 11479199
  41. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.
    Cancer Res. 2001 Aug 15;61(16):5974-8 PMID: 11507037
  42. Delineation of prognostic biomarkers in prostate cancer.
    Nature. 2001 Aug 23;412(6849):822-6 PMID: 11518967
  43. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
    Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74 PMID: 11553815
  44. Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis.
    Cancer Res. 2001 Sep 15;61(18):6885-91 PMID: 11559565
  45. Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation.
    Gynecol Oncol. 2001 Nov;83(2):177-85 PMID: 11606070
  46. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13790-5 PMID: 11707567
  47. Diversity of gene expression in adenocarcinoma of the lung.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13784-9 PMID: 11707590
  48. Multiclass cancer diagnosis using tumor gene expression signatures.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15149-54 PMID: 11742071
  49. Molecular characterization of human meningiomas by gene expression profiling using high-density oligonucleotide microarrays.
    Am J Pathol. 2002 Aug;161(2):665-72 PMID: 12163391
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401994101
Published
2004-06-22
Epub
2004-00-07
Pages
9309-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC438973
Subset
IM
Grants
NIGMS NIH HHS · R01 GM072007-02 · United States
NCI NIH HHS · P30 CA046592 · United States
NIGMS NIH HHS · R01 GM072007 · United States
NCI NIH HHS · 5P30 CA46592 · United States
NCI NIH HHS · P50 CA69568 · United States
NCI NIH HHS · P50 CA069568 · United States
External Links
PubMed source DOI: 10.1073/pnas.0401994101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2