Fig. 3: Evolution of aggressive UM phenotype triggered by PRC1 inhibition. | Nature Communications

Fig. 3: Evolution of aggressive UM phenotype triggered by PRC1 inhibition.

From: Loss of polycomb repressive complex 1 activity and chromosomal instability drive uveal melanoma progression

Fig. 3

a Volcano plots showing differentially expressed genes upon PRT-treatment across five UM cell lines ranked according to their GEP1/GEP2 score (see Supplementary Fig. 5a–c). Fold change for individual genes is shown as a function of significance, -log10(FDR). Genes with FDR value less than 0.05 and fold change greater or less than 1, were highlighted in green and red, respectively. Genes not meeting significance (FDR > 0.05) are shown as gray. Number of genes meeting significance (FDR < 0.05) are annotated per each cell line. b Ratio of GEP1/GEP2 average gene signature expression (gene signatures annotated in Supplementary Data File 1) in low-risk UM cells (92.1) and high-risk UM cells (MP38) upon 24 h DMSO or PRT-treatment; FPKM values obtained from bulk RNA-seq are reported (bar, mean; circles, biological duplicates). c Venn diagram of differentially expressed genes (DEG) upon PRT treatment (red) and between high-risk UM cells (MP38) and low-risk UM cells (92.1) (green). d A schematic showing transcriptional de-repression upon pharmacologic inhibition of PRC1 using PRT (“PRT-geneset” annotated in Supplementary Data File 1). e Expression of the PRT-geneset across individual tumor cells ranked by average imputed expression of the GEP2 gene signature (gene signatures annotated in Supplementary Data File 1) in ascending order from left to right. For each gene, imputed expression was z-normalized across all cells and smoothed using a 20-cell moving average window. Top, filled area plot showing average expression of the GEP2 signature across ranked tumor cells. f Average expression of genes upregulated upon PRT-treatment of 92.1 cells (‘PRT-geneset’) across the 4 molecular TCGA subtypes. Statistical significance tested using one-way ANOVA; p = 9.6 × 10−9; n = 80. Bars, mean of average expression; error bars, standard error of the mean. g Overall survival of (n = 80) TCGA-UM patients with primary tumors stratified by high (top 50th percentile, n = 40) and low (bottom 50th percentile, n = 40) average expression of the “PRT-geneset”. Statistical significance tested using two-sided log-rank test.

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