Identification of key processes underlying cancer phenotypes using biologic pathway analysis

Sol Efroni, Carl F. Schaefer, Kenneth Buetow

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Cancer is recognized to be a family of gene-based diseases whose causes are to be found in disruptions of basic biologic processes. An increasingly deep catalogue of canonical networks details the specific molecular interaction of genes and their products. However, mapping of disease phenotypes to alterations of these networks of interactions is accomplished indirectly and non-systematically. Here we objectively identify pathways associated with malignancy, staging, and outcome in cancer through application of an analytic approach that systematically evaluates differences in the activity and consistency of interactions within canonical biologic processes. Using large collections of publicly accessible genome-wide gene expression, we identify small, common sets of pathways - Trka Receptor, Apoptosis response to DNA Damage, Ceramide, Telomerase, CD40L and Calcineurin - whose differences robustly distinguish diverse tumor types from corresponding normal samples, predict tumor grade, and distinguish phenotypes such as estrogen receptor status and p53 mutation state. Pathways identified through this analysis perform as well or better than phenotypes used in the original studies in predicting cancer outcome. This approach provides a means to use genome-wide characterizations to map key biological processes to important clinical features in disease.

Original languageEnglish (US)
Article numbere425
JournalPLoS One
Volume2
Issue number5
DOIs
StatePublished - May 9 2007
Externally publishedYes

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taxonomic keys
Genes
Phenotype
phenotype
neoplasms
Tumors
Neoplasms
trkA Receptor
CD40 Ligand
Molecular interactions
Calcineurin
Ceramides
Telomerase
telomerase
ceramides
Gene expression
Estrogen Receptors
Genome
gene interaction
genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Identification of key processes underlying cancer phenotypes using biologic pathway analysis. / Efroni, Sol; Schaefer, Carl F.; Buetow, Kenneth.

In: PLoS One, Vol. 2, No. 5, e425, 09.05.2007.

Research output: Contribution to journalArticle

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