Stromal Gene Signatures in Large-B-Cell Lymphomas

作者：Georg Lenz, George W. Wright, Sandeep S. Davé, Wenming Xiao, John Powell, Hong Zhao, Weihong Xu, Bruce K. Tan, Neta Goldschmidt, Javeed Iqbal, Julie Vose, M. Bast, Kai Fu, DD Weisenburger, Timothy C. Greiner, Jamés O. Armitage, Alastair H. Kyle, Lorraine F. May, Randy D. Gascoyne, Joseph M. Connors, Gunhild Trøen, Harald Holte, Stein Kvaløy, Daan Dierickx, G. Verhoef, Jan Delabie, Erlend B. Smeland, Pedro Jares, Antonio Martı́nez, Armando López‐Guillermo, Emili Montserrat, Elı́as Campo, Rita M. Braziel, Thomas P. Miller, Lisa M. Rimsza, James R. Cook, Brad Pohlman, John Sweetenham, Raymond R. Tubbs, Richard I. Fisher, Elena Hartmann, Andreas Rosenwald, German Ott, Müller-Hermelink Hk, David Wrench, T. Lister, Elaine S. Jaffe, Wyndham H. Wilson, Wing C. Chan, Louis M. Staudt · 发表于：New England Journal of Medicine · 年份：2008 · DOI：10.1056/nejmoa0802885 · 被引用次数：1845 · 研究领域：Lymphoma Diagnosis and Treatment、CNS Lymphoma Diagnosis and Treatment、CAR-T cell therapy research

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.