Fig. 3
Tumor branching evolution reveals that intertumoral heterogeneity and the proportion of fibroblasts promote the poor prognosis of high-grade serous ovarian cancer. (A) Overall survival curves showing the prognosis of the three subtypes (G1, G2, and G3) obtained from non-negative matrix factorization (NMF) clustering using the 150 tumor evolution features in TCGA and GEO cohorts. (B) Boxplots showing the immune cell infiltrates ratio in the three distinct malignant subtypes in the significantly enriched patients via xCell (ns, not significant, *P < 0.05, **P < 0.01, and ***P < 0.001). Pairwise comparisons were conducted using the Wilcoxon rank-sum test in the RNA cohort. For the boxplot, the centerline represents the median, and the box limits represent the upper and lower quartiles. (C) Boxplot showing the GSVA enrichment scores in the poorest prognosis using the branch features of tumor evolution analysis in scRNA datasets. Boxplots showing the mean expression level of BR3 genes in the three subtypes of bulk RNA datasets. ns, not significant, *P < 0.05, **P < 0.01, and ***P < 0.001 by Wilcoxon rank-sum test. (D) GO enrichment analysis of upregulated genes of the poorest prognosis group (G1 in TCGA; G2 in the other cohorts). GO:0030198: Extracellular matrix organization, GO:0043062:extracellular structure organization, GO:0071559: Response to transforming growth factor beta, GO:0031589: Cell-substrate adhesion, GO:0060562: Epithelial tube morphogenesis, GO:0010631: Epithelial cell migration, GO:0045123: Cellular extravasation, GO:0061448: Connective tissue development, GO:0048660: Regulation of smooth muscle cell proliferation, GO:0050673: Epithelial cell proliferation, GO:0007043: Cell-cell junction assembly, GO:0032642: Regulation of chemokine production, GO:0007160: Cell-matrix adhesion, GO:0048639: Positive regulation of developmental growth, GO:0016049: Cell growth, GO:0001558: Regulation of cell growth, GO:0042692: Muscle cell differentiation, GO:0030336: Negative regulation of cell migration, GO:0045229: External encapsulating structure organization, GO:0090130: Tissue migration, GO:0032602: Chemokine production.
