Fig. 7
The VAX2-driven mesenchymal development subtype of TNBC exhibits high malignancy and heightened sensitivity to BETi. (a) Clinical data from SYSUCC-TNBC analysis on the impact of VAX2 immunohistochemical staining intensity on patient prognosis. (b) Multivariate Cox model analysis of the effect of VAX2 immunohistochemical staining intensity on OS in SYSUCC-TNBC. (c–e) Effects of VAX2 SE269 excision, direct VAX2 knockdown in CAL51 and MDA468 cell lines, and VAX2 overexpression in MDA231 cells on cell proliferation (c), migration (d), and invasion (e). n = 3 biological independent samples. (f) Tumour growth of the indicated E0771 cells in C57BL/6 mice (n = 7 mice per group). (g) Multiple immunofluorescence analyses showing the effect of VAX2 expression on mCAF infiltration. (h) Sensitivity of wild-type TNBC mesenchymal development subtype cell lines, SE269-deleted lines, and VAX2-knockdown lines to BETi, n = 6 biological independent samples. (i-j) Schematic of JQ1 in vivo therapy experiments (n = 10 mice per group). Blue dashed lines indicate the JQ1 dosing period. (i). Tumor growth curves and weight measurements of CAL51 and modified strains from BALB/c nude mice 30 days after vehicle or JQ1 treatment (j). Error bars represent mean ± SD. The p value in (c, d, e) was caluculated by a two-sided Student's t-test. The p value in (f) and (j) was determined by one-way ANOVA, ** p < 0.01, *** p < 0.001. Data in (c, d, e, h) were representative of three independent experiments. Data in (f, g, i, j) were representative of two independent experiments.