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. 2023 Apr 16;83(12):1953–1967. doi: 10.1158/0008-5472.CAN-22-3848

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©2023 The Authors; Published by the American Association for Cancer Research

This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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Figure 5. Homozygous Keap1R554Q impairs adenocarcinoma progression in the KrasG12D/+; p53fl/fl model. A, Overall survival of KrasG12D/+; p53fl/fl mice with Keap1 mutation. Keap1+/+ (n = 20); Keap1R554Q/+ (n = 11); Keap1R554Q/R554Q (n = 25). B, Overall survival of KrasG12D/+; p53fl/fl mice with Nrf2 mutation. Nrf2+/+ (n = 25); Nrf2D29H/+ (n = 29). ns, not significant [log-rank (Mantel–Cox) test]. C, Representative IHC staining of Nrf2 in KrasG12D/+; p53fl/fl mice with Keap1/Nrf2 mutation. Scale bars, 20 μm. D, H-scores for Nrf2 (nuclear) IHC staining. E, Representative IHC staining of Nrf2 target Nqo1. Scale bars, 20 μm. F, H-scores for Nqo1 (whole cell) IHC staining. C–F, N = 3 mice per genotype and >20,000 tumor cells per mouse. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001 (one-way ANOVA). G, Representative whole-lung hematoxylin and eosin–stained section. Scale bars, 2,000 μm. H, Distribution of tumor grades across Keap1/Nrf2 mutant models. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001 (unpaired t test with Holm–Sidak multiple comparisons test). $, fewer than three tumors detected across all mice. I, Fraction of lung tumor burden by grade (lung tumor area per grade/total lung area). *, P < 0.05; ***, P < 0.001 (unpaired t test with Holm–Sidak multiple comparisons test). $, fewer than three tumors detected across all mice. H and I, n ≥ 9 mice and ≥1,900 tumors per genotype. Only one grade 5 tumor was found in the Keap1R554Q/R554Q cohort, and therefore was excluded from these analyses. — Homozygous Keap1^R554Q impairs adenocarcinoma progression in the Kras^G12D/+; p53^fl/fl model. A, Overall survival of Kras^G12D/+; p53^fl/fl mice with Keap1 mutation. Keap1^+/+ (n = 20); Keap1^R554Q/+ (n = 11); Keap1^R554Q/R554Q (n = 25). B, Overall survival of Kras^G12D/+; p53^fl/fl mice with Nrf2 mutation. Nrf2^+/+ (n = 25); Nrf2^D29H/+ (n = 29). ns, not significant [log-rank (Mantel–Cox) test]. C, Representative IHC staining of Nrf2 in Kras^G12D/+; p53^fl/fl mice with Keap1/Nrf2 mutation. Scale bars, 20 μm. D, H-scores for Nrf2 (nuclear) IHC staining. E, Representative IHC staining of Nrf2 target Nqo1. Scale bars, 20 μm. F, H-scores for Nqo1 (whole cell) IHC staining. C–F,N = 3 mice per genotype and >20,000 tumor cells per mouse. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001 (one-way ANOVA). G, Representative whole-lung hematoxylin and eosin–stained section. Scale bars, 2,000 μm. H, Distribution of tumor grades across Keap1/Nrf2 mutant models. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001 (unpaired t test with Holm–Sidak multiple comparisons test). $, fewer than three tumors detected across all mice. I, Fraction of lung tumor burden by grade (lung tumor area per grade/total lung area). *, P < 0.05; ***, P < 0.001 (unpaired t test with Holm–Sidak multiple comparisons test). $, fewer than three tumors detected across all mice. H and I,n ≥ 9 mice and ≥1,900 tumors per genotype. Only one grade 5 tumor was found in the Keap1^R554Q/R554Q cohort, and therefore was excluded from these analyses.