Diffuse Large B-Cell Lymphoma Outcome Prediction by Gene Expression Profiling and Supervised Machine Learning

Nature Medicine January 2002 Volume 8 Number 1 pp 68 - 74. Published: 2001.12.31

M A Shipp, K N Ross, P Tamayo, A P Weng, J L Kutok, R C T Aguiar, M Gaasenbeek, M Angelo, M Reich, G S Pinkus, T S Ray, M A Koval, K W Last, A Norton, T A Lister, J Mesirov, D S Neuberg, E S Lander, J C Aster & T R Golub

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Abstract

Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We have analyzed the expression of 6817 genes in diagnostic tumor specimens from DLBCL patients who received CHOP-based chemotherapy and have applied a supervised learning prediction method to delineate cured vs. fatal/refractory disease. The algorithm identified 2 categories of patients with dramatically different 5-yr overall survivals (70% vs. 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or die of their disease. Features associated with outcome included differences in genes involved in responses to B-cell receptor signaling as well as serine/threonine phosphorylation pathways and downstream regulators of apoptosis. These data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention.

Keywords: DLBCL cancer lymphoma microarray

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Supplemental Data

Description Link/Filename
News & Views Introduction by L J Van't Veer & D De Jong http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v8/n1/full/nm0102-13.html
Supplemental Information (Microsoft Word) Shipp_et_al_Supplementary_Information_v5.doc
Supplemental Information (pdf) Shipp_et_al_Supplementary_Information_v5.pdf
DLBCL vs. FL morphology res file lymphoma_8_lbc_fscc2_rn.res
DLBCL vs. FL morphology cls file lymphoma_8_lbc_fscc2.cls
DLBCL outcome res file lymphoma_8_lbc_outcome_rn.res
DLBCL outcome cls file lymphoma_8_lbc_outcome.cls
Clinical Data Table lymphoma_clinical_011127.xls
Validation Marker Mapping - UniGene Mapping lymphoma_common_unigene.xls
DLBCL CEL files (DLBC1 - DLBC29) (66M) Lymph_LBC_1-29.CEL.tar.gz
DLBCL CEL files (DLBC30 - DLBC58) (66M) Lymph_LBC_30-58.CEL.tar.gz
FSCC CEL files (FSCC1 - FSCC19) (43M) Lymph_FSCC_1-19.CEL.tar.gz
Expanded Figure 5 from paper Lymphoma_Shipp_et_al_Fig5.xls
README describing downloadable files Readme
Paper (PDF) Shipp_et_al_2002.pdf