Fig. 6: The SUVARness gene signature is predictive for treatment outcome in DLBCL.

a GSEA profiles of TIS up-regulated (SUVARness) genes as shown in Fig. 5a probing Eµ-myc;bcl2 lymphomas TIS vs. untreated in vitro (outer left), SENS Eµ-myc lymphomas NR vs. RP (left), and DLBCL patients cured vs. relapsed in two cohorts (GSE31312, GSE98588; right). b Tumor-free survival in SENS Eµ-myc lymphomas stratified by average expression levels (n = 38 each arm) of the 22 core SUVARness genes (cf. Table S1) commonly selected from the GSEA leading edges (region from the top of the gene list to the enrichment score profile peak position) in (a). c Same as in (b), applying a fully humanized version of the core SUVARness classifier, showing PFS of R-CHOP-treated DLBCL patients (GSE98588). Above median: n = 49 (black line), below median: n = 47 (grey line). d OS for patients stratified as in (c). e GSEA results of core SUVARness-regulated genes in the recently reported newly defined molecular DLBCL cluster subtypes C0–C5 (ref. ¹⁴), comparing each cluster vs. the others. According to Chapuy et al., patients in clusters C0/C1/C4, here marked as SUVARness-enriched, had a significantly better PFS compared to patients in clusters C3/C5 (ref. ¹⁴). n = 137 (n = 6 C0, n = 29 C1, n = 32 C1, n = 28 C3, n = 21 C4, n = 21 C5). f Circular workflow of functional interrogations in mouse models of cancer harboring defined genetic lesions, investigation of genetically unmanipulated mouse tumors in a clinical trial-like setting in vivo, and cross-species application of the genetic determinants of novel biological functions and intervention-evoked dynamic state switches learned therein in corresponding human cancer patient cohorts.