Stromal Gene Signatures in Large-B-Cell Lymphomas

被引：1372

作者：

Lenz, G. ^{[1
]}

Wright, G. ^{[2
]}

Dave, S. S. ^{[1
]}

Xiao, W. ^{[3
]}

Powell, J. ^{[3
]}

Zhao, H. ^{[1
]}

Xu, W. ^{[1
]}

Tan, B. ^{[1
]}

Goldschmidt, N. ^{[1
]}

Iqbal, J. ^{[5
]}

Vose, J. ^{[5
]}

Bast, M. ^{[5
]}

Fu, K. ^{[5
]}

Weisenburger, D. D. ^{[5
]}

Greiner, T. C. ^{[5
]}

Armitage, J. O. ^{[5
]}

Kyle, A. ^{[6
]}

May, L. ^{[6
]}

Gascoyne, R. D. ^{[6
]}

Connors, J. M. ^{[6
]}

Troen, G. ^{[7
]}

Holte, H. ^{[8
]}

Kvaloy, S. ^{[8
]}

Dierickx, D. ^{[11
]}

Verhoef, G. ^{[11
]}

Delabie, J. ^{[7
]}

Smeland, E. B. ^{[9
,10
]}

Jares, P. ^{[12
]}

Martinez, A. ^{[12
]}

Lopez-Guillermo, A. ^{[12
]}

Montserrat, E. ^{[12
]}

Campo, E. ^{[12
]}

Braziel, R. M. ^{[13
,14
]}

Miller, T. P. ^{[14
,15
]}

Rimsza, L. M. ^{[14
,15
]}

Cook, J. R. ^{[14
,17
]}

Pohlman, B. ^{[16
]}

Sweetenham, J. ^{[16
]}

Tubbs, R. R. ^{[14
,17
]}

Fisher, R. I. ^{[14
,18
]}

Hartmann, E. ^{[19
]}

Rosenwald, A. ^{[19
]}

Ott, G. ^{[19
,20
]}

Muller-Hermelink, H. -K ^{[19
]}

Wrench, D. ^{[21
]}

Lister, T. A. ^{[21
]}

Jaffe, E. S. ^{[4
]}

Wilson, W. H. ^{[1
]}

Chan, W. C. ^{[5
]}

Staudt, L. M. ^{[1
]}

机构：

[1] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA

[3] NIH, Bioinformat & Mol Anal Sect, Bethesda, MD 20892 USA

[4] NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[5] Univ Nebraska Med Ctr, Omaha, NE USA

[6] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada

[7] Univ Oslo, Rikshosp Univ Hosp, Pathol Clin, N-0027 Oslo, Norway

[8] Univ Oslo, Rikshosp Univ Hosp, Canc Clin, N-0027 Oslo, Norway

[9] Univ Oslo, Rikshosp Univ Hosp, Canc Res Inst, N-0027 Oslo, Norway

[10] Univ Oslo, Norwegian Radium Hosp, Ctr Canc Biomed, Fac Div, N-0027 Oslo, Norway

[11] Katholieke Univ Leuven, Dept Hematol, Louvain, Belgium

[12] Univ Barcelona, Hosp Clin, Barcelona, Spain

[13] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[14] SW Oncol Grp, Tucson, AZ USA

[15] Univ Arizona, Ctr Canc, Tucson, AZ USA

[16] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA

[17] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA

[18] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY USA

[19] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany

[20] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[21] St Bartholomews Hosp, Canc Res UK, London, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 359卷 / 22期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1056/NEJMoa0802885

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2313 / 2323

页数：11

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