Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Ash A. Alizadeh, Andrew J. Gentles, Alvaro J. Alencar, Chih Long Liu, Holbrook E. Kohrt, Roch Houot, Matthew J. Goldstein, Shuchun Zhao, Yasodha Natkunam, Ranjana H. Advani, Randy D. Gascoyne, Javier Briones, Robert J. Tibshirani, June H. Myklebust, Sylvia K. Plevritis, Izidore S. Lossos, Ronald Levy

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Several gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the "germinal center B cell-like" subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of "cell-of-origin" classification, "stromal signatures," IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.

Original languageEnglish (US)
Pages (from-to)1350-1358
Number of pages9
JournalBlood
Volume118
Issue number5
DOIs
StatePublished - Aug 4 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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