Abstract
Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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APOBEC-3G Deaminase
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Adaptor Proteins, Signal Transducing
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
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Cyclophosphamide / administration & dosage
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Cytidine Deaminase / genetics
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Cytoskeletal Proteins / genetics
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DNA-Binding Proteins / genetics
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Doxorubicin / administration & dosage
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Female
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Forkhead Transcription Factors / genetics
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Gene Expression Profiling*
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Humans
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LIM Domain Proteins
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Lymphoma, Large B-Cell, Diffuse / drug therapy*
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Lymphoma, Large B-Cell, Diffuse / genetics
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Lymphoma, Large B-Cell, Diffuse / immunology
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Lymphoma, Large B-Cell, Diffuse / mortality
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Male
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Metalloproteins / genetics
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Middle Aged
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Multivariate Analysis
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Prednisone / administration & dosage
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Proto-Oncogene Proteins
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Repressor Proteins / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Rituximab
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Vincristine / administration & dosage
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rab GTP-Binding Proteins / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Cytoskeletal Proteins
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DNA-Binding Proteins
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FOXP1 protein, human
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Forkhead Transcription Factors
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LIM Domain Proteins
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LMO2 protein, human
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LPP protein, human
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Metalloproteins
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Proto-Oncogene Proteins
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RAB33A protein, human
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Repressor Proteins
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Rituximab
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Vincristine
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Doxorubicin
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Cyclophosphamide
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APOBEC-3G Deaminase
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APOBEC3G protein, human
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Cytidine Deaminase
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rab GTP-Binding Proteins
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Prednisone