Fig. 1: Acquired resistance to cetuximab is associated with expression changes for metabolism-related genes and proteins. | Nature Communications

Fig. 1: Acquired resistance to cetuximab is associated with expression changes for metabolism-related genes and proteins.

From: PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma

Fig. 1

Growth of cetuximab-sensitive (-S) and -resistant (-R) SCC22b (a) and SC263 cells (b) after treatment with 1 µg/mL cetuximab (CTX) for 96 h (N = 3, n = 6). c General workflow of the integration of SCC22b-S/-R and SC263-S/-R proteomic analysis with a microarray-DNA data-based inference of protein activity by VIPER algorithm. Created in BioRender. https://BioRender.com/d17s016. d Heatmap showing the –log10 transformed enrichment p–values of different gene sets, indicated along the Y-axis, in each of the six identified network clusters (X-axis). A white color reflects a p-value of 0.05, hence all red colors indicate significant interactions. e Dot plot showing –log10 transformed enrichment p-values (X-axis) of gene sets (Y-axis) in clusters 1 (top panel) and 6 (bottom panel) of the protein-protein interaction network. Each dot is color-coded according to the enrichment odds ratio (OR). Small black dots indicate the enrichment p-value of that gene set in the entire network, in contrast to the cluster specific enrichment. A p-value of 0.05 is indicated using a vertical dashed line. f Minimal spanning tree representation of the protein-protein interaction network of cluster 1. Proteins in red and blue are respectively up- and downregulated in cetuximab-resistant HNSCC cells. The shape of the nodes reflects the protein class (i.e. circles=metabolic seeds, triangles=non-metabolic seeds). Grey nodes are intermediate proteins, that were identified using the shortest-paths algorithm and that are necessary to connect all proteins in the network. g Bar plot showing the node degree distribution of all proteins in the network of cluster 1. The node degree, being the number of connections each protein has in the network, is shown in the X-axis, the different proteins are listed along the Y-axis. Grey bars reflect intermediate proteins. Data are plotted as the means ± SEM (a, b). N indicates the number of independent biological experiments and n indicates the number of technical replicates. Significance was determined by two-way ANOVA with Sidák’s multiple comparison test (a, b). ***P < 0.001; ns not significant. Source data are provided as a Source Data file.

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