A strategy for full interrogation of prognostic gene expression patterns

Exploring the biology of diffuse large B cell lymphoma

Lisa Rimsza, Joseph M. Unger, Margaret E. Tome, Michael L. LeBlanc

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Gene expression profiling yields quantitative data on gene expression used to create prognostic models that accurately predict patient outcome in diffuse large B cell lymphoma (DLBCL). Often, data are analyzed with genes classified by whether they fall above or below the median expression level. We sought to determine whether examining multiple cut-points might be a more powerful technique to investigate the association of gene expression with outcome. Methodology/Principal Findings: We explored gene expression profiling data using variable cut-point analysis for 36 genes with reported prognostic value in DLBCL. We plotted two-group survival logrank test statistics against corresponding cut-points of the gene expression levels and smooth estimates of the hazard ratio of death versus gene expression levels. To facilitate comparisons we also standardized the expression of each of the genes by the fraction of patients that would be identified by any cut-point. A multiple comparison adjusted permutation p-value identified 3 different patterns of significance: 1) genes with significant cut-point points below the median, whose loss is associated with poor outcome (e.g. HLA-DR); 2) genes with significant cut-points above the median, whose over-expression is associated with poor outcome (e.g. CCND2); and 3) genes with significant cut-points on either side of the median, (e.g. extracellular molecules such as FN1). Conclusions/Significance: Variable cut-point analysis with permutation p-value calculation can be used to identify significant genes that would not otherwise be identified with median cut-points and may suggest biological patterns of gene effects.

Original languageEnglish (US)
Article numbere22267
JournalPLoS One
Volume6
Issue number8
DOIs
StatePublished - 2011
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
lymphoma
Gene expression
B-lymphocytes
Genes
Cells
Gene Expression
Biological Sciences
gene expression
genes
Gene Expression Profiling
HLA-DR Antigens
statistics
Hazards
death
Statistics
Survival
Molecules
methodology

ASJC Scopus subject areas

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

Cite this

A strategy for full interrogation of prognostic gene expression patterns : Exploring the biology of diffuse large B cell lymphoma. / Rimsza, Lisa; Unger, Joseph M.; Tome, Margaret E.; LeBlanc, Michael L.

In: PLoS One, Vol. 6, No. 8, e22267, 2011.

Research output: Contribution to journalArticle

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