Figure 7. Immunohistochemical analysis of SOX4 expression in patients with human breast cancer reveals a positive correlation with decreased survival, increased metastasis and elevated blood vessel density.
(A–B) Representative images of SOX4 expression in invasive lobular carcinoma (ILC, classical and pleomorphic) and invasive ductal carcinoma (IDC, low-grade tumor and high-grade tumor) cases in the tissue microarray (TMA) cohort. (C–E) Kaplan-Meier curves for cumulative (cum) survival for patients with high or low nuclear SOX4 expression for the total cohort, ILC and IDC breast cancers. Indicated p-values were calculated using the Log-rank test. (F) Representative images of CD34 staining in SOX4HI and SOX4LO tumors as identified previously in TMA analysis. Arrows indicate blood vessels. (G) Quantitative analysis of CD34 staining in 17 SOX4HI and 17 SOX4LO ductal carcinomas. (Student t-test, *p-value<0.05). (H) Schematic model for the pro-angiogenic function of SOX4 during breast cancer progression. The SOX4 transcription factor binds to regions of active/open chromatin and subsequently acts as positive regulator of many genes involved in tumorigenesis, such as EDN1. Upregulation of ET-1 contributes to the increase of neovascularization, which ultimately may facilitate tumor cell intravasation and growth factor accessibility.
Figure 7—figure supplement 1. SOX4 mRNA expression correlates with decreased patient survival in both ER positive and negative breast cancers.
Figure 7—figure supplement 2. Gene set enrichment analysis on RNA-seq data derived from conditional activation of SOX4 in HMLE cells.
