The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab.
Résumé
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.
Mots clés
Aged
Aged
80 and over
Antibodies
Monoclonal
Antineoplastic Combined Chemotherapy Protocols
Cyclophosphamide
Cytidine Deaminase
Cytoskeletal Proteins
DNA-Binding Proteins
Forkhead Transcription Factors
Gene Expression Profiling
Humans
Lymphoma
Large B-Cell
Diffuse
Middle Aged
Multivariate Analysis
Prednisone
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction
Vincristine
rab GTP-Binding Proteins
Domaines
Biochimie, Biologie Moléculaire
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