ArticleEpigenetics2011
Regulation of KEAP1 expression by promoter methylation in malignant gliomas and association with patient's outcome.
Article in Epigenetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it.
- KEAP1 promoter hypermethylation in human cancers: a meta-analysis of case-control studies.International journal of clinical oncology · 2026Pooled it
- Review
- COX-2 Inhibition in Glioblastoma Cells Counteracts Resistance to Temozolomide by Inducing Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Nrf2 Signaling in Renal Cell Carcinoma: A Potential Candidate for the Development of Novel Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.Cell death & disease · 2024Article
- Temozolomide Resistance in Glioblastoma by NRF2: Protecting the Evil.Biomedicines · 2023Review
- Review
- An update of Nrf2 activators and inhibitors in cancer prevention/promotion.Cell communication and signaling : CCS · 2022Review
- Crosstalk of Epigenetic and Metabolic Signaling Underpinning Glioblastoma Pathogenesis.Cancers · 2022Review
- The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.Medical oncology (Northwood, London, England) · 2022Review
- Multifaceted Roles of the KEAP1-NRF2 System in Cancer and Inflammatory Disease Milieu.Antioxidants (Basel, Switzerland) · 2022Review
- NRF2: KEAPing Tumors Protected.Cancer discovery · 2022Article
- Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.Frontiers in pharmacology · 2022Review
- The Emerging Roles and Therapeutic Implications of Epigenetic Modifications in Ovarian Cancer.Frontiers in endocrinology · 2022Review
- Integrated analysis of patients with KEAP1/NFE2L2/CUL3 mutations in lung adenocarcinomas.Cancer medicine · 2021Article
- Activation of the NRF2 antioxidant program sensitizes tumors to G6PD inhibition.Science advances · 2021Article
- Article
- Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid-induced osteonecrosis of the femoral head.Clinical and translational medicine · 2021Article
- Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.Molecules (Basel, Switzerland) · 2021Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In light with the view that KEAP1 loss of function may impact tumour behavior and modify response to chemotherapeutical agents, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and after treatment with 5-azacytidine (P=0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n=70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35-22.74). Our results further suggest that KEAP1 expression is epigenetically regulated. In addition we demonstrated that KEAP1 is frequently methylated in malignant gliomas and a predictor of patient's outcome.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.