Fig. 4

The transcriptomic landscape of FGFRi sensitive and resistant HNSCC cell models differs profoundly. A Workflow of RNA-sequencing analysis in 3D lrECM HNSCC cell models upon FGFRi treatment (2 µM; DMSO as control) with or without single 6 Gy X-ray irradiation. Images were partly adapted from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License. B Heatmap of 5000 most variable expressed genes between all treated and control samples. Columns represent biological replicates (n = 4), rows represent z-score normalized gene expression data, both hierarchically clustered. C Overrepresentation analyses of strongly differential expressed genes (DEG, log2FC ≥|2|) between UT-SCC 33 and UM-SCC 10a cell models at basal/untreated conditions. Selected functional enrichments of individual database analyses (KEGG, GO, Reactome) are presented by gene counts and adjusted p-values. Complete results are listed in Table S3. D Principal component analysis of the top 5000 most variably expressed genes in each cell model upon indicated treatment conditions. Colored ellipses outline directions of treatment-induced transcriptomic shifts compared to controls. E Normalized enrichment score (NES) summary of six gene set enrichment analyses (GSEA) for the FGFR signaling signature (Table S3) in each DEG comparison group (IR, 6 Gy X-ray irradiated; FGFRi, FGFR inhibitor treatment; FGFRi/IR, combined treatment). Significance levels (p.adj, adjusted p-value ≤ 0.05; n.s., non-significant) are indicated by triangle size. Triangle direction represents enrichment or suppression in the corresponding DEG comparison group. F Functional characterization of treatment-induced effects between the DEG comparison groups (IR; FGFRi; FGFRi/IR) for each cell model. All DEG (adjusted p-value ≤ 0.05) were included. Selected functional enrichments of individual database analyses (KEGG, GO, Reactome) are presented by gene counts and adjusted p-values. Complete results are listed in Table S3