Prediction of survival in diffuse large B-cell lymphoma based on the expression of two genes reflecting tumor and microenvironment
Menée sur trois cohortes indépendantes incluant un total de 545 patients atteints d'un lymphome diffus à grandes cellules B, cette étude montre que l'expression d'un gène dans les cellules tumorales et l'expression d'un gène dans le micro-environnement tumoral sont associées à la survie
Several gene expression signatures predict survival in diffuse large B cell lymphoma (DLBCL), but the lack of practical methods for genome scale analysis has limited translation to clinical practice. We built and validated a simple model employing one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LMO2 was validated as an independent predictor of survival and 'Germinal Center B-cell' subtype. Expression of TNFRSF9 from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T-cells. A model integrating these two genes was independent of 'cell of origin' classification, 'stromal signatures', IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in three independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin fixed specimens from a new validation cohort of 147 patients with DLBCL. Thus, measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.
Blood , résumé, 2011