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Fig. 5 | Journal of Experimental & Clinical Cancer Research

Fig. 5

From: Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer

Fig. 5

Genomic profile and drug sensitivity of PDCs, and functional validation using cell lines. A Therapeutic groups were categorized into two arms. The first arm was BASELINE (yellow) to POST1 (light green). The second was BASELINE to POST2 (dark green) to POST3 (orange). B Heatmap presenting the mutation profile, RNA subtype, and tumor mutation burden (TMB) of each group. In the POST1 group, the red asterisk indicates the EGFR double mutation including T790M. C Heatmap of the DEGs for the four groups. DEGs and pathways (GSEA P < 0.1) for each group are denoted on the right. D Two scatter plots of scores extracted from EGFR-TKI resistance pathway gene pairs. ERBB2 and MET were upregulated in the POST2 group (dotted circle), and YAP/TAZ-AXL activated in the POST3 group (dotted circle). R indicates Pearson’s correlation coefficient, and the P value was acquired using the Wilcoxon rank-sum test from the AUC values. E Volcano plot to test drug sensitivity for each group. The x-axis is log2 fold change (FC) and the y-axis is P-value. F Drug response curves based on the viability of H1975, H1975_OR3, and OR4 cells treated with osimertinib. G Bar plots of YAP1 and its target gene expressions. Fold increases (x-axis) in mRNA expression in each gene (y-axis) were assessed using RT-PCR in H1975, H1975_OR3, and OR4 cells. H The protein level expression assessment in three cells using western blot analysis. I Cell migration across the transmembrane. Cell morphology images are shown from three cases. The bar plot indicates the average number of migrating cells (y-axis) for each condition (x-axis). J EpCAM expression (x-axis) determined using flow cytometry. Graphs were analyzed using the FlowJo program. K Drug response curves treated with XAV939. The AUC of each condition for XAV939 is shown in the panel. All experiments were performed in quadruplicate. The values represent the mean ± SEM (Student’s t-test, *P < 0.05; **P < 0.01; ***P < 0.001)

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