NCOA4-mediated ferritinophagy expression signature is a prognostic marker in human PDAC. A, Relative clonogenic growth of KPCY (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre; Rosa26YFP/YFP) murine PDAC cells expressing doxycycline (Dox)-inducible lentiviral short hairpin RNAs (shRNA): ishControl, ishNcoa4-1, and ishNcoa4-2 treated with or without doxycycline (100 ng/mL). Error bars ± SD; triplicate wells of a representative experiment of 3 independent experiments; significance determined by a two-sided t test. ns = not significant: P > 0.1; *, P < 0.05; **, P < 0.01. B,In vivo subcutaneous tumor growth in C57BL/6 mice of KPCY ishControl versus ishNcoa4-1 cells with and without doxycycline-containing food. Doxycycline was initiated after tumors reached an average of 75 mm3 (day 0 on graph). Error bars ± SEM; n = 6 mice per group. Significance was determined by a one-sided t test. ^, P < 0.1; *, P < 0.05; **, P < 0.01. C, Survival analysis with the log-rank test of a ferritinophagy gene expression signature (NCOA4, FTH1, TAX1BP1, and RB1CC1) in PDAC using the TCGA data set. D, Survival analysis with the log-rank test of a ferritinophagy gene expression signature (NCOA4, FTH1, TAX1BP1, and RB1CC1) in PDAC using the Cao et al. 2021 data set (37).