Stromal gene signatures in large-B-cell lymphomas

G. Lenz, G. Wright, S. S. Dave, W. Xiao, J. Powell, H. Zhao, W. Xu, B. Tan, N. Goldschmidt, J. Iqbal, J. Vose, M. Bast, K. Fu, D. D. Weisenburger, T. C. Greiner, J. O. Armitage, A. Kyle, L. May, R. D. Gascoyne, J. M. ConnorsG. Troen, H. Holte, S. Kvaloy, D. Dierickx, G. Verhoef, J. Delabie, E. B. Smeland, P. Jares, A. Martinez, A. Lopez-Guillermo, E. Montserrat, E. Campo, Rita Braziel, T. P. Miller, L. M. Rimsza, J. R. Cook, B. Pohlman, J. Sweetenham, R. R. Tubbs, R. I. Fisher, E. Hartmann, A. Rosenwald, G. Ott, H. K. Muller-Hermelink, D. Wrench, T. A. Lister, E. S. Jaffe, W. H. Wilson, W. C. Chan, L. M. Staudt

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1036 Scopus citations

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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ASJC Scopus subject areas

  • Medicine(all)

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Lenz, G., Wright, G., Dave, S. S., Xiao, W., Powell, J., Zhao, H., Xu, W., Tan, B., Goldschmidt, N., Iqbal, J., Vose, J., Bast, M., Fu, K., Weisenburger, D. D., Greiner, T. C., Armitage, J. O., Kyle, A., May, L., Gascoyne, R. D., ... Staudt, L. M. (2008). Stromal gene signatures in large-B-cell lymphomas. New England Journal of Medicine, 359(22), 2313-2323. https://doi.org/10.1056/NEJMoa0802885