Figure 3 from PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer

PPARD expression is linked to metabolic switch and EMT in patients with PDAC. A, Expression levels of PPARD in PDAC tumors (T) vs. surrounding normal tissue (N) included in the TCGA and GTEx projects. B, Patients were dichotomized for PPARD expression [higher (n = 58) and lower (n = 81) expression compared with the mean; RNA-seq V2 RSEM values]. Kaplan–Meier curves for disease-free survival are shown. Dotted lines denote the confidence intervals. Survival, 19.48 vs. 13.53 months. C and D, A TMA with 108 cases was stained by IHQ using an anti–PPARδ antibody. Representative images depicting different signal intensities (weak vs. strong) and localizations (nuclear vs. cytoplasmatic) are shown in C. Magnification, ×400. Scale bar, 50 μm. Arrows, stained cancer cells. D, Signal intensity was scored by Allred immunoreactive score, and patients were dichotomized into low (n = 34; scores 0–6) vs. high (n = 59; scores 7–8) PPARδ expression groups. Kaplan–Meier curves for overall survival are shown. Dotted lines denote the confidence intervals. Survival, 17.5 vs. 11 months. E, Correlation between PPARD tumor expression levels family members and an EMT-associated signature composed of SNAI1, SNAI2, and ZEB1. F, Gene sets enriched in the transcriptional profile of tumors belonging to the top PPARD high-expression group compared with the bottom low-expression group in the TCGA data series (PAAD, pancreatic adenocarcinoma). Shown are the normalized enrichment score (NES) values for each pathway using the Hallmark gene sets, meeting the significance criteria: nominal P value of < 0.05, FDR < 25%. G, Enrichment plot for TNFα, EMT, glycolysis, and hypoxia hallmarks in PPARD-high vs. -low samples shown in F, indicating values of normalized enrichment score and FDR q values. H, Representative images of costaining of PPARδ (nuclear and cytoplasmatic, red) and HIF1α (nuclear brown) by IHQ in several patients shown in C and D. Magnification, ×400. Scale bar, 50 μm. Arrows, costained cancer cells. See also Supplementary Fig. S6.