MOESM8 of Transcriptomic profiling and quantitative high-throughput (qHTS) drug screening of CDH1 deficient hereditary diffuse gastric cancer (HDGC) cells identify treatment leads for familial gastric cancer

Additional file 8: Figure S6. A, Target enrichment for compounds with CRC −1.1, −1.2, −2.1, or −2.2 and delta logAC50 (SB.mhdgc-1 logAC50–SB.msgc-1 logAC50) < −1. −log p values were calculated as described in materials and methods based on the total number of compounds targeting a gene or mechanism. B, LogAC50 distributions of compounds that show CRC −1.1, −1.2, −2.1, or −2.1 and logAC50 <−1 organized by enriched target class in c.1380delA CDH1 SB.mhdgc-1 versus SB.msgc-1 gastric cancer cells. Box plots of median logAC50 values of select target classes showing enrichment in c.1380delA CDH1 SB.mhdgc-1 (red plots) and SB.msgc-1 (blue plots). C, Concomitant dysregulation of target genes and selective activity of MIPE compounds in c.1380delA CDH1 SB.mhdgc-1 versus SB.msgc-1 gastric cancer cells. Genes with greater than two-fold expression difference in c.1380delA CDH1 SB.mhdgc-1 compared to SB.msgc-1 cells and which are direct targets of compounds in MIPE Oncology 4 are shown. Genes that are downregulated in c.1380delA CDH1 SB.mhdgc-1 compared to SB.msgc-1 cells are represented by green dots; red dots represent upregulated genes (log10 fold change indicated on the right). Overlaid are boxplots for difference in logAC50 (LAC50) SB.mhdgc-1–SB.msgc-1 for all compounds in MIPE Oncology 4 per target (top) or maximum response (bottom).