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. 2020 Sep 22;9(9):904. doi: 10.3390/antiox9090904

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Correlation between KEAP1 CpGs methylation and transcript levels of NRF2 or its target genes in LUAD and LUSC KRAS wild-type/KRAS mutated subpopulations. The KEAP1 gene structure, is shown in the middle, including exons (sky blue boxes) and introns (brown boxes), as well as two CpG islands: CGI-1 and CGI-2 (both underlined with green bars). A total of 16 CpG sites, marked with green circles, are indicated from 5′ to 3′ genomic localization (listed below). A filled rhombus, corresponding to a KEAP1 CpG site, depicts a significant inverse (blue square) or direct (red square) correlation (R ≤ −0.1; p < 0.05) between methylation and transcript levels of NRF2 or its target genes in LUAD KRAS wild-type/KRAS mutated (A) and particularly in LUSC KRAS wild-type/KRAS mutated (B), in contrast to an empty rhombus indicating no significant correlation. Abbreviations: EX, exon; Intr, intron; CGI-1, CpG Island 1; CGI-2, CpG Island 2; LUSC, lung squamous cell carcinoma; LUAD, lung adenocarcinoma; No-mts, non-metastatic disease stages.