Abstract
Nuclear factor, erythroid 2 like 2 (NFE2L2, NRF2) is a transcription factor that regulates various antioxidant enzymes. It plays a vital physiological role in regulating oxidative stress and inflammatory response. However, the roles of NFE2L2 in human cancers are still unclear. Our study is aimed at analyzing the prognostic value of NFE2L2 in pan-cancer and at revealing the relationship between NFE2L2 expression and tumor immunity. The present study revealed that NFE2L2 was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels and DNA methyltransferase expression in human pan-cancer. In particular, pan-cancer survival analysis indicated that NFE2L2 expression was associated with adverse outcomes—overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI)—in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), and pancreatic adenocarcinoma (PAAD) patients. A positive relationship was also found between NFE2L2 expression and immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), LGG, liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Additionally, NFE2L2 expression was positively correlated with the immune score and the expression of immune checkpoint markers in LGG. In conclusion, these results indicate that transcription factor NFE2L2 is a potential prognostic biomarker and is correlated with immune infiltration in LGG.
Highlights
Nuclear factor, erythroid 2 like 2 (NFE2L2) is a redoxsensitive transcription factor localized mainly in the cytoplasm
NFE2L2 expression was significantly higher in CHOL and lung squamous cell carcinoma (LUSC) tissues than in normal tissues. It was significantly lower in BLCA, breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), KICH, kidney renal clear cell carcinoma (KIRC), KIRP, liver hepatocellular carcinoma (LIHC), LUAD, prostate adenocarcinoma (PRAD), READ, (b)
We found that NFE2L2 expression was significantly correlated with the levels of 6 types of infiltrating immune cells (B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils) in BRCA, COAD, KIRC, lower grade glioma (LGG), and PRAD
Summary
Erythroid 2 like 2 (NFE2L2) is a redoxsensitive transcription factor localized mainly in the cytoplasm. It is ubiquitously expressed in the esophagus, thyroid, and other tissues [1, 2]. The redox subtype of lung squamous cell carcinoma (LUSC) is driven by genomic mutations in the NFE2L2/KEAP1 complex [9]. Programmed death-1 (PD-1) and programmed death-ligand-1 (PD-L1) inhibitors have been found to induce tumor cell apoptosis by blocking the PD-1/PD-L1 signaling pathway, playing an effective antitumor role in lung cancer and melanoma [13, 19,20,21]. The role and underlying mechanisms of NFE2L2 in tumor immunity are unknown
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