Fig. 5. Increased expression of MYC-SL nucleocytoplasmic transport genes is associated with poor prognosis in human HCC and XPO1 inhibition reduces growth of patient-derived xenografts.
a Association of MYC-SL RNA transport genes with disease outcome in human HCC. Survival z-scores were calculated based on Cox Regression using TCGA data on liver hepatocellular carcinoma (LIHC RNA-seq and clinical data). Positive z-scores are associated with poor prognosis. Left: Z-scores of MYC-SL RNA transport genes (red) are compared to the genome-wide random distribution (black). Right: Prognostic association of individual MYC-SL RNA transport genes in human HCC. b Survival analysis of TCGA LIHC data subdivided by expression of MYC hallmark genes (HALLMARK_MYC_TARGETS_V2, M5928) assessed by singscore92. Graphs show upper and lower quartiles (p-value and HR from two-sided logrank test). c Survival analysis of subgroups with high and low MYC activity shown in (b) based on XPO1 RNA expression level (p-value and HR from two-sided logrank test). d Representative images of MYC expression in two biologically independent HCC PDX models assessed by immunohistochemistry. At least three high power field images were aquired per PDX. Scale bar = 20 μm. e Relative tumor volume of HCC patient-derived xenografts (PDX) with high or low MYC expression in NSG mice treated with vehicle (grey symbols) or XPO1 inhibitor Selinexor (red symbols). PDX samples obtained from two HCC patients (PDX-37, and PDX-58) were examined over two independent experiments (PDX-37: vehicle (n = 11 mice), XPO1i (n = 11 mice); PDX-58: vehicle (n = 6 mice), XPO1i (n = 4 mice). Lines are means +/− SEM. For this figure, source data are provided as a Source Data file.