ArticleEpigenetics2013
Aberrant Keap1 methylation in breast cancer and association with clinicopathological features.
Article in Epigenetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- KEAP1 promoter hypermethylation in human cancers: a meta-analysis of case-control studies.International journal of clinical oncology · 2026Pooled it
- Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026Review
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- The cross-talk between NRF2 and apoptosis in cancer.Medical molecular morphology · 2025Review
- TNFAIP2 promotes NF-κB signaling mediate lymph node metastasis of oral squamous cell carcinoma by protecting IKKβ from ubiquitin proteasome degradation.Cell communication and signaling : CCS · 2025Article
- Article
- Mechanistic analysis of enhancer sequences in the estrogen receptor transcriptional program.Communications biology · 2024Article
- AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.Cell death & disease · 2024Article
- High Expression of NRF2 and Low Expression of KEAP1 Predict Worse Survival in Patients With Operable Triple-Negative Breast Cancer.Journal of breast cancer · 2023Article
- Nutriepigenomics in Environmental-Associated Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Post-translational modifications of Keap1: the state of the art.Frontiers in cell and developmental biology · 2023Review
- An update of Nrf2 activators and inhibitors in cancer prevention/promotion.Cell communication and signaling : CCS · 2022Review
- NRF2: KEAPing Tumors Protected.Cancer discovery · 2022Article
- Critical appraisal of epigenetic regulation of galectins in cancer.International journal of clinical oncology · 2022Review
- Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.Frontiers in pharmacology · 2022Review
- Article
- Nuclear Factor Erythroid 2-Related Factor 2 in Regulating Cancer Metabolism.Antioxidants & redox signaling · 2020Review
- Review
- Epigenetic Scanning ofAntioxidants (Basel, Switzerland) · 2020Article
- Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keap1 (Kelch-like ECH-associated protein 1) is an adaptor protein that mediates the ubiquitination/degradation of genes regulating cell survival and apoptosis under oxidative stress conditions. We determined methylation status of the KEAP1 promoter in 102 primary breast cancers, 14 pre-invasive lesions, 38 paired normal breast tissues and 6 normal breast from reductive mammoplasty by quantitative methylation specific PCR (QMSP). Aberrant promoter methylation was detected in 52 out of the 102 primary breast cancer cases (51%) and 10 out of 14 pre-invasive lesions (71%). No mutations of the KEAP1 gene were identified in the 20 breast cancer cases analyzed by fluorescence based direct sequencing. Methylation was more frequent in the subgroup of patients identified as ER positive-HER2 negative tumors (66.7%) as compared with triple-negative breast cancers (35%) (p = 0.05, Chi-square test). The impact of the interactions between Er, PgR, Her2 expression and KEAP1 methylation on mortality was investigated by RECPAM multivariable statistical analysis, identifying four prognostic classes at different mortality risks. Triple-negative breast cancer patients with KEAP1 methylation had higher mortality risk than patients without triple-negative breast cancer (HR = 14.73, 95%CI: 3.65-59.37). Both univariable and multivariable COX regressions analyses showed that KEAP1 methylation was associated with a better progression free survival in patients treated with epirubicin/cyclophosfamide and docetaxel as sequential chemotherapy (HR = 0.082; 95%CI: 0.007-0.934). These results indicate that aberrant promoter methylation of the KEAP1 gene is involved in breast cancerogenesis. In addition, identifying patients with KEAP1 epigenetic abnormalities may contribute to disease progression prediction in breast cancer patients.
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