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. 2024 Jun 28;75:103261. doi: 10.1016/j.redox.2024.103261

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© 2024 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Fig. 3 — Tumors with Nrf2^E79Q activated post-DMBA display increased tumor progression and enriched Nrf2 target gene expression. (A) Representative examples of an H&E-stained papilloma, papilloma with an area of SCC, micro-invasive SCC and invasive SCC. The scale bars are equal to 500um (papilloma, papilloma with SCC, microinvasive SCC and invasive SCC) and 250um (100× original magnification of papilloma with SCC) (B) Ratio of SCC to papilloma and ratio of papilloma with SCC to papilloma analyzed from tumors collected from 9 K14CreER^tam and 11 K14CreER^tam;LSL-Nrf2^E79Q/wt mice. * Denotes p = 0.13 Fisher's Exact Test and p = 0.08 Risk Difference. (C) Volcano plot and heatmap of tumor RNAseq data from K14CreER^tam;LSL-Nrf2^E79Q/wt skin tumors compared to K14CreER^tam skin tumors. Each column represents a tumor from a different mouse. (D) IPA pathway analysis of RNAseq data reveals, of the significantly enriched pathways, the top pathways predicted to be activated (z-score ≥2.0 are predicted to be activated) and pathways predicted to be inhibited (z-score ≤2.0) in K14CreER^tam;LSL-Nrf2^E79Q/wt skin tumors compared to K14CreER^tam skin tumors. Right tailed Fisher Exact Test with Benjamini-Hochberg (B–H) multiple hypothesis testing-corrected p-value (E) IPA's upstream regulator analysis of RNAseq data reveals top upstream transcription regulators, upstream regulators with z-scores ≥2.0 are predicted to be activated and upstream regulators with z-scores ≤2.0 are predicted to be inhibited based on observed gene expression changes in tumors of K14CreER^tam;LSL-Nrf2^E79Q/wt mice compared to K14CreER^tam mice. Right tailed Fisher Exact Test with Benjamini-Hochberg (B–H) multiple hypothesis testing-corrected p-value (F) Tumors from K14CreER^tam;LSL-Nrf2^E79Q/wt epidermis expresses Nrf2^E79Q transcripts. Each bar represents a tumor from a different mouse. (G) OIS-PRM targeted proteomics showed a significant increase in the Nrf2 score in tumors from K14CreER^tam;LSL-Nrf2^E79Q/wt mice compared to tumors from K14CreER^tam mice. * denotes p ≤ 0.05 via Mann-Whitney U test.