Figure 4.

An ICD-related signature predicts clinical outcome in patients with multiple myeloma (MM) after BTZ treatment. A, Log₂ fold-change (log2FC) values for 90 genes, as determined by RNA-seq analysis, in 5TGM1^WT or 5TGM1 Calr^KO tumors growing in immunocompetent C57BL/KaLwRij mice after two BTZ treatments (0.5 mg/kg). Columns represent the conditions, and rows are those differentially expressed genes (DEG) in the BTZ-treated cohort compared with the CNT cohort (n = 3 mice per group). FC > 1.5 and FDR < 0.05. B and D, Analysis of the human orthologs of this 90-gene murine ICD signature was performed in CD138⁺ multiple myeloma cells from two independent BTZ-treated cohorts of patients with multiple myeloma: IFM/DFCI 2009 dataset (n = 327; B) and GSE9782 (n = 152; D). Heatmaps identified three clusters of patients with multiple myeloma showing high (red), medium (blue), and low (green) expression of these signature genes. C and E, Kaplan–Meier plots show OS for the three patient clusters identified by expression of the 90 ICD gene signature. Red, blue, and green curves represent OS of patients with high, medium, and low ICD signature expression, respectively. Log-rank test P values for IFM/DCFI 2009 dataset and GSE9782 dataset are 0.01 and 0.047.