Fig. 2: PROX1 suppresses liver cancer formation and progression.
a, PROX1 expression in tumors from patients with HCC and paired normal tissue24. b, PROX1 protein in patients with HCC liver tumors and adjacent nontumor tissues (n = 15). c, Survival of patients with HCC stratified by PROX1 expression levels (40% high-expression cutoff)32. d, Survival of patients with HCC ranked by PROX1 amplification status25,26,27,28,29,30,31. e, Confluency of Hep3B cancer cells upon PROX1 shRNA-KD or OE for 7 days normalized to uninduced controls (n = 3). f, Differential ATAC–seq accessibility in Hep3B cells upon PROX1 OE for 2 days (n = 3; adjusted P < 0.05). g, Prox1 and hepatocyte signature expression across 7,793 single cells in healthy (day 0) and MYC-induced mouse HCC model (day 28)35. h, Mouse livers following HDTVI-mediated Myc OE and Trp53 KO with constitutive Prox1 OE (n = 5). i, Percentage of GFP+ tumors in mice treated as in h (n = 4). j, Survival of mice treated as in h following constitutive Prox1 OE (n = 5) or doxycycline-inducible late Prox1 OE (n = 4) at day 14 compared to control (n = 5 for constitutive OE and n = 3 for late OE). k, HDTVI-induced liver tumors following Kras(G12D) OE and Trp53 KO with constitutive Prox1 OE (OE; n = 4). l, Percentage of GFP+ tumors in mice treated as in k (n = 4). m, Survival of mice treated as in k following constitutive Prox1 OE or control (n = 4). Scale bar = 10 mm (h,k). Bar graphs and scatter plots show mean, error bars = s.d., boxplots show median and IQR and whiskers = 1.5× IQR from specified replicates. Unpaired two-tailed t test (a,b,i,l), log-rank test (c,d,j,m) and two-tailed one-sample t test (e). P values are displayed. ROI, region of interest; HR, hazard ratio; KO, knockout; KD, knockdown; OE, overexpression; IQR, interquartile range.
