Fig. 7: TI cell programs are enriched in HNSC and associated with poor prognosis.

a mTORC1 and YAP pathway enrichment in malignant tumors (T) compared to matched normal adjacent tissue (N) by single sample GSEA (ssGSEA) among TCGA-HNSC cohort subjects (n = 43 T and 44 N tissue samples from 44 unique human subjects). Two-tailed Mann-Whitney test: ****p < 0.0001. b Correlation of YAP and mTORC1 pathway activity by ssGSEA among TCGA-HNSC samples (n = 520). Kaplan-Meier plots for overall survival among TCGA-HNSC (n = 520) subjects stratified by greater than (red) or less than (blue) median (c) YAP and (d) mTORC1 pathway activity. Kaplan-Meier plots for disease-free survival among TCGA-HNSC (n = 393) subjects stratified by greater than (red) or less than (blue) median (e) YAP and (f) mTORC1 pathway activity. Please see Supplementary Data 1, for gene set details. g Left: Weighted gene co-expression network analysis (WGCNA) heatmap displaying topological overlap matrix dissimilarity indices among genes in TI cluster cells. Right: Table of WGCNA modules and selected genes identified by Metascape and Enrichr, see Supplementary Data 6 for details. (h) Module enrichment in malignant tumors (T) compared to matched normal adjacent tissue (N) by ssGSEA among TCGA-HNSC subjects (n = 43 subjects with matched T and N samples). Two-tailed Mann Whitney test: **p < 0.01, ****p < 0.0001. i–k Kaplan-Meier plots for overall survival (n = 520) among TCGA-HNSC subjects stratified by greater than (red) or less than (blue) median enrichment for the (i) G1/S, (j) Cell Motility & Migration, and (k) Focal Adhesion TI cell modules. For panels c–f and i–k, p-values were calculated by Mantel-Cox log-rank tests. Boxplots in a and h show median, interquartile range (IQR), and range. All panels display biological replicates (individual human tissue samples as described in panel a). See Source Data for panels a–f, h–k.