| Diffuse Large B-Cell Lymphoma Outcome Prediction by Gene Expression Profiling and Supervised Machine Learning
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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. |
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| Authors | Margaret A. Shipp1, Ken N. Ross2, Pablo Tamayo2, Andrew P. Weng3, Jeffery L. Kutok3, Ricardo C.T. Aguiar1 , Michelle Gaasenbeek2, Michael Angelo2, Michael Reich2, Geraldine S. Pinkus3, Tane S. Ray2,8, Margaret A. Koval1, Kim W. Last4, Andrew Norton5, T. Andrew Lister4, Jill Mesirov2, Donna S. Neuberg1, Eric S. Lander2,6, Jon C. Aster3, Todd R. Golub1,2
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
2Whitehead Institute for Biomedical Research/Massachusetts Institute of Technology Center for Genome Research, Cambridge, MA
3Brigham and Women's Hospital, Harvard Medical School, Boston, MA
4ICRF Medical Oncology Unit, St. Bartholemew's Hospital, London
5Pathology Unit, St. Bartholemew's Hospital, London
6Department of Biology, Massachusetts Institute of Technology, Cambridge, MA
8Dept. of Comp. Sci., Maths & Physics, University of the West Indies, Bridgetown, Barbados |
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| Publication Date | 1/1/2002 |
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Contact emails |
golub@genome.wi.mit.edu
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| Bibiliographic information | Nature Medicine, Volume 8, Number 1, January 2002. |
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| Keywords | DLBCL; lymphoma; cancer; microarray |
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