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

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2008 Jul 11

PMID 18615101

Citations 43

Authors

J-P Jais

C Haioun

T J Molina

D S Rickman

A de Reynies

F Berger

C Gisselbrecht

J Briere

F Reyes

P Gaulard

P Feugier

E Labouyrie

H Tilly

C Bastard

B Coiffier

G Salles

K Leroy

Affiliations

Soon will be listed here.

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.

Citing Articles

Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma.

Park J, Chung S, Lee Y, Shin H, Hur M, Cho H Clin Mol Hepatol. 2023; 29(3):794-809.

PMID: 37196991 PMC: 10366791. DOI: 10.3350/cmh.2023.0057.

Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms.

Taghi Khani A, Kumar A, Sanchez Ortiz A, Radecki K, Aramburo S, Lee S Commun Biol. 2023; 6(1):295.

PMID: 36941341 PMC: 10027679. DOI: 10.1038/s42003-023-04667-8.

Artificial Intelligence Predicted Overall Survival and Classified Mature B-Cell Neoplasms Based on Immuno-Oncology and Immune Checkpoint Panels.

Carreras J, Roncador G, Hamoudi R Cancers (Basel). 2022; 14(21).

PMID: 36358737 PMC: 9657332. DOI: 10.3390/cancers14215318.

APOBEC3G protects the genome of human cultured cells and mice from radiation-induced damage.

Britan-Rosich Y, Ma J, Kotler E, Hassan F, Botvinnik A, Smith Y FEBS J. 2022; 290(7):1822-1839.

PMID: 36325681 PMC: 10079569. DOI: 10.1111/febs.16673.

Oncological Treatment-Related Fatigue in Oncogeriatrics: A Scoping Review.

Andre L, Antherieu G, Boinet A, Bret J, Gilbert T, Boulahssass R Cancers (Basel). 2022; 14(10).

PMID: 35626074 PMC: 9139887. DOI: 10.3390/cancers14102470.

References

Irizarry R, Hobbs B, Collin F, Beazer-Barclay Y, Antonellis K, Scherf U . Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2):249-64. DOI: 10.1093/biostatistics/4.2.249. View

Harrell Jr F, Lee K, Mark D . Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996; 15(4):361-87. DOI: 10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4. View

Nyman H, Adde M, Karjalainen-Lindsberg M, Taskinen M, Berglund M, Amini R . Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood. 2007; 109(11):4930-5. DOI: 10.1182/blood-2006-09-047068. View

Fabiani B, Delmer A, Lepage E, Guettier C, Petrella T, Briere J . CD10 expression in diffuse large B-cell lymphomas does not influence survival. Virchows Arch. 2004; 445(6):545-51. DOI: 10.1007/s00428-004-1129-7. View

Winter J, Weller E, Horning S, Krajewska M, Variakojis D, Habermann T . Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006; 107(11):4207-13. PMC: 1895783. DOI: 10.1182/blood-2005-10-4222. View

Natkunam Y, Farinha P, Hsi E, Hans C, Tibshirani R, Sehn L . LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab. J Clin Oncol. 2007; 26(3):447-54. DOI: 10.1200/JCO.2007.13.0690. View

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

Rosenwald A, Wright G, Chan W, Connors J, Campo E, Fisher R . The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346(25):1937-47. DOI: 10.1056/NEJMoa012914. View

de Jong D, Rosenwald A, Chhanabhai M, Gaulard P, Klapper W, Lee A . Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications--a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol. 2007; 25(7):805-12. DOI: 10.1200/JCO.2006.09.4490. View

10.

Jacobsen M, Repsilber D, Gutschmidt A, Neher A, Feldmann K, Mollenkopf H . Ras-associated small GTPase 33A, a novel T cell factor, is down-regulated in patients with tuberculosis. J Infect Dis. 2005; 192(7):1211-8. DOI: 10.1086/444428. View

11.

Barrans S, Fenton J, Banham A, Owen R, Jack A . Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004; 104(9):2933-5. DOI: 10.1182/blood-2004-03-1209. View

12.

Segal M . Microarray gene expression data with linked survival phenotypes: diffuse large-B-cell lymphoma revisited. Biostatistics. 2005; 7(2):268-85. DOI: 10.1093/biostatistics/kxj006. View

13.

Harris N, Jaffe E, Diebold J, Flandrin G, Muller-Hermelink H, Vardiman J . World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999; 17(12):3835-49. DOI: 10.1200/JCO.1999.17.12.3835. View

14.

Banham A, Connors J, Brown P, Cordell J, Ott G, Sreenivasan G . Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2005; 11(3):1065-72. View

15.

Smith M . Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003; 22(47):7359-68. DOI: 10.1038/sj.onc.1206939. View

16.

Mounier N, Briere J, Gisselbrecht C, Emile J, Lederlin P, Sebban C . Rituximab plus CHOP (R-CHOP) overcomes bcl-2--associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003; 101(11):4279-84. DOI: 10.1182/blood-2002-11-3442. View

17.

Zehetmayer S, Bauer P, Posch M . Two-stage designs for experiments with a large number of hypotheses. Bioinformatics. 2005; 21(19):3771-7. DOI: 10.1093/bioinformatics/bti604. View

18.

Guo B, Sallis R, Greenall A, Petit M, Jansen E, Young L . The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3. Mol Cell Biol. 2006; 26(12):4529-38. PMC: 1489114. DOI: 10.1128/MCB.01667-05. View

19.

Monti S, Savage K, Kutok J, Feuerhake F, Kurtin P, Mihm M . Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood. 2004; 105(5):1851-61. DOI: 10.1182/blood-2004-07-2947. View

20.

Cartron G, Watier H, Golay J, Solal-Celigny P . From the bench to the bedside: ways to improve rituximab efficacy. Blood. 2004; 104(9):2635-42. DOI: 10.1182/blood-2004-03-1110. View