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PMID: 21670469 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Blood ·Vol. 118 ·No. 5 ·2011-08-04 ·Pages 1350-8

Alizadeh AA, Gentles AJ, Alencar AJ, Liu CL, Kohrt HE, Houot R, Goldstein MJ, Zhao S, Natkunam Y, Advani RH, Gascoyne RD, Briones J, Tibshirani RJ, Myklebust JH, Plevritis SK, Lossos IS, Levy R

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor/genetics,physiology Child Cohort Studies DNA-Binding Proteins/genetics,physiology Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, Neoplasm Genetic Predisposition to Disease Genetic Testing Humans LIM Domain Proteins Lymphoma, Large B-Cell, Diffuse/diagnosis,genetics,mortality Metalloproteins/genetics,physiology Middle Aged Neoplasms/genetics,pathology Prognosis Proto-Oncogene Proteins Survival Analysis Tumor Microenvironment/genetics,immunology Tumor Necrosis Factor Receptor Superfamily, Member 9/genetics,physiology Young Adult
Chemicals
Adaptor Proteins, Signal Transducing Biomarkers, Tumor DNA-Binding Proteins LIM Domain Proteins LMO2 protein, human Metalloproteins Proto-Oncogene Proteins TNFRSF9 protein, human Tumor Necrosis Factor Receptor Superfamily, Member 9
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Alizadeh Ash A
Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, USA. [email protected]
Gentles Andrew J
Alencar Alvaro J
Liu Chih Long
Kohrt Holbrook E
Houot Roch
Goldstein Matthew J
Zhao Shuchun
Natkunam Yasodha
Advani Ranjana H
Gascoyne Randy D
Briones Javier
Tibshirani Robert J
Myklebust June H
Plevritis Sylvia K
Lossos Izidore S
Levy Ronald
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2011-03-345272
Email
[email protected]
Published
2011-08-04
Epub
2011-00-13
Pages
1350-8
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC3152499
Subset
IM
Grants
NIAID NIH HHS · T32 AI007290 · United States
NCI NIH HHS · U56 CA112973 · United States
NCI NIH HHS · P01 CA034233 · United States
NCI NIH HHS · U54CA149145 · United States
NCI NIH HHS · P01CA34233 · United States
NCI NIH HHS · U54 CA149145 · United States
NCI NIH HHS · R01 CA109335 · United States
NCI NIH HHS · U56-CA112973 · United States
NCI NIH HHS · CA109335 · United States
External Links
PubMed source DOI: 10.1182/blood-2011-03-345272 PMC Full Text View journal details
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