Fig. 6: Engagement of FAK and YAP transcriptional programs in patient NSCLC specimens of residual disease.

a Normalized expression of YAP signature genes across patient specimen classified as TN, RD or progressive disease (PD) using previously published single cell RNA-seq (scRNA-seq) data¹. The YAP signature determined by genes within the YAP-5SA_UP gene set that are significantly upregulated across PC9, H3122, and H358 DTPs, and were also differentially upregulated in the RD treatment timepoint. The sequencing data were filtered to limit analyzes to malignant lung epithelial cells only (N cells: TN = 621, RD = 484, PD = 138). P-values obtained from two-sided Dunn’s test with Bonferroni adjustment. The box plot displays 25th (lower bound), 50th (centre, median), and 75th (upper bound) percentiles, with whiskers (minima (bottom), maxima (top)) extending 1.5 * IQR. b Average expression of individual YAP signature genes highlighted across TN, RD, and PD treatment groups. c Immunohistochemistry staining for YAP in patient specimens classified as TKI treatment naïve (TN) or collected at residual disease upon treatment with targeted inhibitors (RD). Quantification of nuclear levels (% nuclear) by automated image analysis. Arrows indicate YAP-positive tumor cell nuclei, scale bar: 20 μm. Statistical analysis by two-sided t-test. *** p = 0.0007, n = 18 independent experiments. d Single-cell RNAseq analysis of clinical samples showed enrichment of the FAK signature in the residual disease state. The significant FAK features include NEDD9, PTPRE, MAP1B, PTRF and NOV. Violin plot data points are single cells’ mean expression of FAK signature. P-values obtained from two-sided Dunn’s test with Bonferroni adjustment.