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E. Derenzini et al.
tion did not provide any significant PFS or OS advantage compared to standard chemoimmunotherapy in the MBN-Sig high subgroup (Online Supplementary Figure S8A and B). The aberrant activation of NF-kB observed in lym- phoma is associated with decreased abundance of IkB-α (which is encoded by the NFKBIA gene).41,42 Since borte- zomib is known to increase IkB-α levels by blocking its
ubiquitination and therefore inhibiting NF-kB activity,43-45 we next examined the Sha dataset18,27 performing an exploratory ad hoc analysis to investigate the impact of the addition of bortezomib to standard R-CHOP (RB-CHOP) in the MBN-Sig high subset (characterized by decreased NFKBIA levels).18,27 Interestingly, RB-CHOP determined a significant PFS advantage in the MBN-Sig high population
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Figure 4. Real-life applicability of the MBN signature. (A) Heatmap representing the three informative genes of the MBN signature (MBN-Sig) shown as rows and dif- fuse large B-cell lymphoma (DLBCL) tissue samples shown as columns in the real-life cohort of 102 patients, with the actual MBN-Sig and the predicted MBN-Sig class based on the application of a random forest (RF) model built on the discovery cohort on the top of the heatmap. (B) Violin plot showing the fractions of false predictions (false positive [FP], and false negative [FN]) as well as true predictions (true positive [TP], and true negative [TN]) in the real-life cohort by applying a three-gene RF model. (C) ROC curve of the real-life cohort using RF classifier. (D) Overall survival (OS) curve of the real-life cohort (n=102) based on the predicted MBN-Sig class. P-value was calculated with the log rank test.
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