Fig. 5

Smoke exposure activates Nrf2 targets consistently upregulated in cisplatin resistant HNSCC. A NRF2 ssGSEA scores are significantly higher in both smoke-naïve (UMSCC47 and UDSCC2) and chronically exposed cell lines (SCC152 and SCC154) following an 8 h bolus of acute smoke. **** adj p value < 0.0001. B Venn diagram illustrating the number of NRF2 signature genes significantly elevated in 12 clones derived from 3 different cisplatin (CDDP)-resistant HNSCC cell line genetic backgrounds, 4 HPV-associated HNSCC cell lines treated with smoke, and their overlap. A total of 36 common NRF2-target genes were significantly elevated in clones from all 3 different CDDP resistant cell lines (HN30, HN31, and PCI13) and 11 of these genes (listed to the right) overlapped with all 4 HPV-associated HNSCC cell lines exposed to smoke. C Volcano plot of UDSCC2 proteins as a function of fold change and log10 p value at 10% smoke exposure generated using JMP Pro version 17 (SAS Institute Inc., 2023). A cutoff of 1.25 fold change (equivalent to 0.322 log2 fold change) and a false discovery rate (FDR) of 0.05 (equivalent to -log10(p value) of 1.30) were applied. The y-axis represents -log10 p value, while the x-axis displays log2 fold change. Targets associated with metabolism, immunity, and Nrf2 signaling are highlighted. Downregulated targets are indicated in blue, and upregulated targets are shown in red. D Heatmap of proteins significantly elevated (FDR = 0.1) by smoke exposure (10%) from the Molecular Signature Database NRF2 pathway (i.e., NFE2L2.V2), which were identified by mass spectrometry