ArticleThe oncologist2020
NFE2L2/KEAP1 Mutations Correlate with Higher Tumor Mutational Burden Value/PD-L1 Expression and Potentiate Improved Clinical Outcome with Immunotherapy.
Article in The oncologist, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis.PloS one · 2020Pooled it
- A 5-Genomic Mutation Signature Can Predict the Survival for Patients With NSCLC Receiving Atezolizumab.Frontiers in immunology · 2021Trial
- Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer.Genes and immunity · 2026Article
- Article
- Clinicopathological characteristics of patients with inoperable non-small cell lung cancer harboring circulating NRF2 pathway mutations.The Journal of pathology · 2026Article
- A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification.Redox biology · 2026Review
- Chemo-Radio-Immunotherapy Strategies to Prevent Immune Resistance in Non-Small Cell Lung Cancer.Cancers · 2025Review
- Effects of the Pharmacological Modulation of NRF2 in Cancer Progression.Medicina (Kaunas, Lithuania) · 2025Review
- Survival impact of a KEAP1-NFE2L2 radiomics model in PDL1 ≥ 50% non-small cell lung cancer treated with pembrolizumab: the PEMBROMIC study.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression.Communications biology · 2025Article
- Decoding the tumor immune microenvironment in lung squamous cell carcinoma: characteristics, regulatory mechanisms, and future directions in immunotherapy.Translational lung cancer research · 2025Review
- Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role ofJournal for immunotherapy of cancer · 2025Review
- Tumour- and Non-Tumour-Associated Factors That Modulate Response to PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer.Cancers · 2025Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- Molecular characterization of EBV-associated primary pulmonary lymphoepithelial carcinoma by multiomics analysis.BMC cancer · 2025Article
- Differential impact of intratumor heterogeneity (ITH) on survival outcomes in early-stage lung squamous and adenocarcinoma based on tumor mutational burden (TMB).Translational lung cancer research · 2024Article
- Prevalence and Associations of Co-occurrence ofGlobal medical genetics · 2024Article
- Combining Genomic Biomarkers to Guide Immunotherapy in Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- The Dual Role of NRF2 in Colorectal Cancer: Targeting NRF2 as a Potential Therapeutic Approach.Journal of inflammation research · 2024Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAbnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo- and radiotherapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. MATERIALS AND
methodsWe investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9,040 patients with cancer, and relevance analysis with PD-L1 expression was performed in 3,457 patients. The Memorial Sloan Kettering Cancer Center (MSKCC) database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets.
resultsNFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation incidences occurred in lung squamous cell carcinoma (LUSC) at 19.16% (NFE2L2) and 10.31% (KEAP1). We confirmed that higher TMB value and PD-L1 expression were associated with NFE2L2/KEAP1 mutations compared with wild-type, especially in non-small lung cancer. MSKCC database analysis showed the improved survival of patients with NFE2L2/KEAP1 mutant with immunotherapy compared with other treatments (median overall survival 22.52 VS 12.89, p = .0034). Real-world evidence further confirmed the efficacy of immunotherapy in the mutant population.
conclusionOur study revealed that patients with NFE2L2/KEAP1 mutant could achieve improved outcomes from immunotherapy than the other treatments. These findings may broaden the application of immune checkpoint blockade to patients harboring NFE2L2/KEAP1 mutations. IMPLICATIONS FOR PRACTICE: NFE2L2/KEAP1 alterations occur frequently in multiple cancer types and are associated with poor prognosis; however, the efficacious strategy to inhibit this pathway in cancer is poorly understood. This study was designed to analyze the mutational characteristics of NFE2L2/KEAP1 alterations in 9,243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma at 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher tumor mutational burden value and programmed death-ligand 1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in the NFE2L2/KEAP1 mutant population.
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