Fig. 7

In vitro resistance signatures predict clinical outcome and clinically relevant target genes in HNSCC patient cohorts. A Workflow of defining clinical outcome and clinically relevant targets identified in the FGFRi-induced adaptive resistance response in UM-SCC 10a cells. Images were partly adapted from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License. B Stratification of HPV-negative HNSCC patients from the training cohort (TCGA, n = 280 patients with available clinical endpoints and target gene expression) with the indicated signature-based risk scores (median cut-off) for overall (OS) and progression-free survival (PFS). Hazard ratios of high-risk patients (red curves) and log-rank test p-values for the comparison of high- and low-risk groups are indicated together with 95% confidence intervals in Kaplan–Meier curves including patient numbers at risk. Signature genes and coefficients are listed in Table S3. C Radiotherapy-treated (RT) and non-RT subcohorts of the HPV-negative HNSCC training cohort (RT, n = 181 patients; non-RT, n = 99 patients) are stratified with the PFS signature-based risk score (median cut-off) for PFS. Hazard ratios of high-risk patients (red curves) and log-rank test p-values for the comparison of high- and low-risk groups are indicated together with 95% confidence intervals in Kaplan–Meier curves including patient numbers at risk. D Spearman correlations of derived pathway activities with the corresponding expression of OS/PFS signature genes in either HPV-negative HNSCC TCGA patients (left; n = 415) or single HNSCC cells (right; n = 1891 cells from n = 10 patients; GSE103322; scRNA, single cell RNA-sequencing). Correlations are hierarchically clustered and annotated with adjusted p-values for correlation significance (***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05). E Interaction network of OS and PFS signature genes and kinase inhibitor targets. STRING database was used to discover interconnections between the targets of identified resistance-overcoming kinase inhibitors (see Fig. 6C) and predicted functional partners. The evidence color key for protein- and gene-level connections is indicated. F Interaction network of OS and PFS signature genes and kinase inhibitor targets. GeneMania database was applied to uncover interconnections between the targets of identified resistance-overcoming kinase inhibitors (see Fig. 6C) in radial layout. Evidence color key for pathway, protein- and gene-level connections is shown