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.
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.
Jais
J-P
JP
Service de Biostatistique, AP-HP, hôpital Necker, Paris, France.
Haioun
C
C
Molina
T J
TJ
Rickman
D S
DS
de Reynies
A
A
Berger
F
F
Gisselbrecht
C
C
Brière
J
J
Reyes
F
F
Gaulard
P
P
Feugier
P
P
Labouyrie
E
E
Tilly
H
H
Bastard
C
C
Coiffier
B
B
Salles
G
G
Leroy
K
K
D000071480:APOBEC-3G Deaminase; D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003564:Cytidine Deaminase / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D060588:LIM Domain Proteins; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality; D008297:Male; D008667:Metalloproteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage; D020691:rab GTP-Binding Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C103594:LPP protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; C105244:RAB33A protein, human; D012097:Repressor Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D020691:rab GTP-Binding Proteins; D011241:Prednisone