Figure 4 from Epithelial–Mesenchymal Transition and Stress Adaptations Underlie Yttrium-90 Resistance in Liver Cancer Cell Lines

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Abstract
90Y-resistant and -sensitive cell lines demonstrate distinct patterns of biological process enrichment after 90Y microsphere treatment. A, Volcano plot of log2 FC vs. −log10P value of genes upregulated (red) and downregulated (blue) after 90Y microsphere treatment in select 90Y-resistant cell lines (SK-Hep1, SNU-449, and SNU-387). B, GSEA of Hallmark pathways demonstrates upregulation of pathways involved with inflammation and immune response after treatment in the 90Y-resistant group, such as IFNγ response (mean log2FC = 7.4), among others. C, Consistent with Hallmark IFNγ and IFNα enrichment, KEGG and Reactome pathways associated with cytokine signaling and antigen presentation were upregulated after treatment with 90Y. D, Volcano plot of log2 FC vs. −log10P value of genes upregulated (red) and downregulated (blue) after 90Y microsphere treatment in select 90Y-sensitive cell lines (PLC/PRF/5 and HepG2). E, GSEA of Hallmark pathways demonstrates downregulation of many of the inflammatory and immune response–related pathways that were upregulated in the resistant cell lines, including IFNγ response (mean log2 FC = −4.3,) and IFNα response (mean log2 FC = −4.7). No Hallmark pathways demonstrated significant upregulation after treatment in 90Y-sensitive cells. F, KEGG and Reactome pathway analysis corroborates downregulation of interferon- and antigen presentation–associated pathways, along with those involved with growth signaling such as MAPK (mean log FC = −4.01) and TGFβ (mean log FC = −2.62). Numbers next to each gene set bar represent FDR. Significance set at FDR 2. Heterogeneous activation of stress and survival pathways after 90Y microsphere treatment across different liver cancer cell lines. Significant variation in Hallmark gene sets (G) IFNγ, (H) IFNα, (I) TNFα signaling, (J) hypoxia, (K) myogenesis, (L) p53 pathway, (M) oxidative phosphorylation, and (N) DNA repair, showing heterogeneity in stress and survival pathway activation across cell lines after 90Y microsphere treatment.