NFE2L2 Is a Potential Prognostic Biomarker and Is Correlated with Immune Infiltration in Brain Lower Grade Glioma: A Pan-Cancer Analysis

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.

Pan‐Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy

“…Pan-cancer analysis could reveal the similarities and differences between different cancers and provide deep insights for the design of cancer prevention and personalized treatment strategies. A growing number of recent studies focused on genome-wide pan-cancer analysis to reveal gene mutations, RNA changes, and cancer-driving genes related to the initiation and development of cancer, which are of great significance for the early diagnosis of cancer and the identification of sensitive biomarkers [ 23 , 24 ]. The present study first comprehensively examined the expression of HSF1 in a pan-cancer dataset.…”

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

“…In addition, the overexpression of DNAJB6 leads to radiosensitization of glioblastoma cells 28 . Among the other eight risk‐associated genes, NFE2L2, also known as Nrf2, mediated oxidative stress and inflammatory response 29,30 . Activation of Nrf2‐Keap1 signalling up‐regulates system Xc‐, which is critical for glutathione peroxidase 4 (GPX4).…”

“…28 Among the other eight risk-associated genes, NFE2L2, also known as Nrf2, mediated oxidative stress and inflammatory response. 29,30 Activation of Nrf2-Keap1 E-F) KEGG pathway analysis based on DEGs in TCGA and CGGA signalling up-regulates system Xc-, which is critical for glutathione peroxidase 4 (GPX4). GPX4 negatively regulates ferroptosis by limiting ROS production and reducing iron intake.…”

Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer

“…Pan-cancer analysis focused on whole genome can reveal genes that are associated with the occurrence and development of cancer, providing insights into cancer diagnosis, monitoring and treatment ( 28 – 30 ). By analyzing NOS3 mRNA levels in normal tissues from GTEx, we found that NOS3 was expressed at the highest level in the spleen and was expressed at the lowest level in the blood.…”