Fig. 7: Human HCC patients mutated in RNF43 and/or ZNRF3 present lipid metabolic alterations and poor prognosis. | Nature Communications

Fig. 7: Human HCC patients mutated in RNF43 and/or ZNRF3 present lipid metabolic alterations and poor prognosis.

From: RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state

Fig. 7: Human HCC patients mutated in RNF43 and/or ZNRF3 present lipid metabolic alterations and poor prognosis.The alternative text for this image may have been generated using AI.

a–e Clinical data, whole genomic sequencing and RNAseq data were downloaded from ICGC database and used to determine the prognosis and expression pattern of human tumours mutated in RNF43 and/or ZNRF3 or other WNT pathway components (APC, AXIN1 or CTNNB1). Full details in “Methods”, Supplementary Fig. 8 and Supplementary Data 6. a Experimental design. b Survival analysis after Cox proportional hazards model found a significant interaction with gender, tumour stage and WNT mutation status. All covariates passed the proportional hazards test except WNT mutation. The graph shows the survival analysis of HCC patients with ZNRF3 (ZNRF3, left) or RNF43 or ZNRF3 (RorZ, right) mutations compared to patients with no-WNT mutations (No-WNT). p Values obtained by Wald statistic, CI 95%. c, d Differential gene expression for patients with RorZ and R&Z mutations compared to non-WNT mutants (other w/o Wnt mutation). c A multiple regression model indicated an interaction between WNT mutation status and the signatures of RNF43 or ZNRF3 patients. Note that the presence of WNT mutation (WNT + RorZ) negatively impacts the expression of RorZ patients, with gene sets positively enriched in RorZ mutants becoming negatively enriched. d Significantly enriched (p value <0.05, two-sided permutation test) gene sets in R&Z and RorZ-mutated patients compared to patients with no-WNT mutations. e Comparison between the mouse differentially expressed genes including or excluding TCF4 targets and the signatures of patients with mutations in R&Z, RorZ and WNT (APC, CTNNB1 or AXIN1). The table represents the GSEA (NES) of the DE genes in R&Zdel (3 and 7 months homeostasis or 170 days after damage, including or excluding TCF4 targets) against WNT, R&Z or RorZ human liver tumour signatures. NES scores are presented as a heatmap where red is positively enriched and blue is negatively enriched. Note the significant correlation. f Human liver organoids from healthy donors or patients with liver cancer (mixed subtype, CHC and mutations or not in RNF43) were grown and stained for neutral lipids (Bodipy, Green). Representative images from n = 2 independent experiments. Red, F-actin staining. White, Dapi. Scale bar, 60 μm (top panel); 15 μm (bottom panel).

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