Fig. 8: Matrix organization drives a pro-metastatic transcriptional program.
a Venn diagram showing Mechano-Inflammatory signature (MIS) derived from 4599 cells extracted from TB and DIF and from HT1080 treated with PI for 24 h. b Overlapping genes from (a) - conserved signature- were scored on the Visium array spots in a representative section of human melanoma lymph node metastasis. Annotations correspond to TB and IF areas. n = 4 slices were analysed. Box plot shows the comparison between TB and IF annotations. n = 12 TB annotations and n = 12 IF annotations were analysed. c Volcano plot showing DEGs upon IF and TB comparison from spatial transcriptomics defined annotations. Highlighted in red DEGs that present average log2 fold change >0.5 and -log10 adjusted p-value. d Heatmap shows median scaled by row, displaying Gene Ontology Biological Pathways (GOBP) and Molecular Functions (GOMF) terms separated by regions (TB and IF) and slices from Visium array analysed in melanoma metastasis samples. Z-score scale. e Representative merged multiplex images of primary and metastatic lesions of melanoma tumours. (bottom) Inset of merged multiplex. Nuclei were visualized with Haematoxylin stain (blue). Scale bar: 100 µm. Scale bar insets: 20 µm. f H-score quantification (0-300) of YAP1, p65 and pSTAT3 in the primary and metastatic lesions. n = 53 primary and 45 metastatic lesions. g Kaplan-Meier curve showing overall survival with the quantification of amoeboid cells YAP1, p65 and pSTAT3 positive in the DIF area (left). Kaplan-Meier curve displays the overall survival comparing high and low fibre alignment (right). One-way ANOVA with Tukey post-hoc test (f). Data displayed as violin plots showing individual data points and medians (f). Cartoons in Fig. 8 (b, e) Created in BioRender. Maiques, O. (2024) https://BioRender.com/h15l089.
