Figure 4

Signature construction of ferroptosis genes. (A) Unmonitored clustering of overlapping ferroptosis subtype-related genes in TCGA datasets to attribute patients to different genomic subtypes, named as ferroptosis gene cluster A, B and C. Patient annotations were utilized by the gene clusters, ferroptosis subtypes, TCGA molecular patterns, stage of tumor, grade, histology, status of survival, gender and age. (B) Kaplan–Meier curves suggested that ferroptosis genomic phenotypes were significantly relevant to the 406 patients' survival in TCGA: BLCA dataset, among the cohort, 149 patients were classified to cluster A, 137 patients were classified to cluster B and 120 patients were classified to cluster C (p = 0.055, Log-rank test). (C) The results of 38 ferroptosis-related genes in these gene clusters. The interquartile range of values was represented by the boxes' upper and lower ends, the median value is represented by the lines in the boxes, and outliers were shown by dots in black. The value of p is graphically shown by asterisks, of which * means that p is less than 0.05, ** means less than 0.01 and *** means less than 0.001. The test called one-way ANOVA was applied to check group diversity among these ferroptosis forms statistically. (D) The changes of ferroptosis clusters, TCGA molecular patterns, ferroptosis gene cluster and FerrScore shown by alluvial diagram. (E) Spearman analysis showing the connection between FerrScore and the known gene features in TCGA: BLCA dataset. Blue color represented negative correlation and red color represented positive correlation. (F) Diversities of FerrScore in these gene clusters. The difference of the gene clusters was compared statistically with the Kruskal–Wallis test (p less than 0.05). (G) Diversities of FerrScore in these ferroptosis subtypes in TCGA: BLCA dataset (p less than 0.05, Kruskal–Wallis test). (H) Diversities of stroma-activated pathways in groups of high and low FerrScore. EMT, epithelial-mesenchymal transition; Pan-F-TBRS, pan-fibroblast transforming growth factor (TGF)-β response signature. The interquartile value ranges were indicated by boxes lower and upper ends. The median value was indicated by those lines in the boxes, and outliers were shown with dots of black color. The value of p was graphically shown by asterisks, (***:p less than 0.001).