Stromal Gene Signatures in Large-B-Cell Lymphomas
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Abstract
BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
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The record
- Venue
- New England Journal of Medicine
- Topic
- Lymphoma Diagnosis and Treatment
- Field
- Medicine
- Canadian institutions
- University of British Columbia
- Funders
- Allos TherapeuticsNational Cancer InstituteNational Institutes of HealthGenentechCelgeneBiogenAmgen
- Keywords
- VincristineMedicineRituximabCHOPPrednisoneLymphomaCyclophosphamideDoxorubicinChemotherapyDiffuse large B-cell lymphomaCancer researchB cellOncologyStromal cellInternal medicineImmunologyAntibody
- Has abstract in OpenAlex
- yes