Figure 4.

Global proteomic analysis reveals PRC2 loss enhances tumor growth pathways and promotes immune evasion. A, Heatmap depicting Z-score for proteomic data, for proteins with P < 0.05 between conditions. B and C, GSEA for selected annotated gene sets run using the GSEA preranked tool, with all identified proteins ordered by differential expression between MPNST_LOSS versus MPNST_RET. Proteins showing increased expression in MPNST_LOSS have positive enrichment values and are shown in B. Those with decreased expression in MPNST_LOSS have negative enrichment values and are shown in C. NES, normalized enrichment score. D, Heatmap depicting Z-scores for all MHC protein groups identified across proteomic dataset, ordered with MPNST_RET (left) and MPNST_LOSS (right). Class I MHC proteins are at the top and class I are at the bottom. E, IHC staining for MHC class I (top) and MHC class II (bottom) from representative sections of MPNST_LOSS (left) and MPNST_LOSS (right). In MPNST_LOSS, HLA-A, B, C staining is largely confined to blood vessels, whereas in MPNST_RET, membranous staining is visible in tumor cells as well. MHC class II, represented with HLA-DR staining, is essentially absent in MPNST_LOSS, with only rare, positive-staining antigen-presenting cells. In MPNST_RET, these cells are more numerous. The IHC findings agree with the quantitative values seen across the dataset in the MS analysis.