Fig. 6: GPX4 is a prognostic marker in human PDAC.

a Upregulation of GPX4 and TMEM173 gene expression within the tumor from PDAC patients compared to normal controls using datasets from The Cancer Genome Atlas (TCGA) (*P < 0.001; one-tailed t test). The data are presented as box-and-whisker plots. Boxes represent the median and the 25th and 75th percentiles. b Pearson correlation assay between KRAS, CD163, TMEM173, and GPX4 gene expression in PDAC patient TCGA datasets. c Kaplan–Meier survival analysis with one-sided log-rank test of GPX4 and TMEM173 gene expression in PDAC patients using TCGA datasets. d Schematic depicting the role of high-iron diets or Gpx4 depletion in Kras-driven PDAC. The induction of ferroptosis by either high-iron diets or Gpx4 depletion promotes oxidized nucleobase (e.g., 8-OHG) release and thus activates the TMEM173-dependent DNA sensor pathway, which finally results in macrophage infiltration and activation during Kras-driven PDAC. Consequently, macrophage depletion or pharmacological and genetic inhibition of the 8-OHG-TMEM173 pathway suppresses ferroptosis-mediated pancreatic tumorigenesis.