Abstract
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 using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI).
LIM domain only 2
(
LMO2
) was validated as an independent predictor of survival and the “germinal center B cell–like” subtype. Expression of
tumor necrosis factor receptor superfamily member 9
(
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 2 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 3 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. We conclude that the 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.
