ArticleCell reports. Medicine2023
Silencing of genes by promoter hypermethylation shapes tumor microenvironment and resistance to immunotherapy in clear-cell renal cell carcinomas.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Integrative omics profiling of CRELD2 in ccRCC: a nexus of genetics, prognosis, and tumor microenvironment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- MiT fusions, TSC1-TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa.Nature communications · 2026Article
- Unveiling the epigenetic landscape: transforming renal cell carcinoma treatment.Clinical epigenetics · 2026Review
- Epigenomic subtypes and prognostic methylation signatures in clear cell renal cell carcinoma.Clinical epigenetics · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Promoter Hypermethylation-Driven NPHS2 Silencing Promotes Immune Escape and Sunitinib Resistance in Clear Cell Renal Cell Carcinoma.Oncology research · 2026Article
- Article
- Comprehensive omics-based classification system in adult patients with B-cell acute lymphoblastic leukemia.Molecular oncology · 2025Article
- ALAD as a prognostic biomarker regulates metabolism and immune responses in renal cell carcinoma through multi-omics analysis.Translational oncology · 2025Article
- FBLN2 promoter hypermethylation: a negative prognostic biomarker and anti-PD-1 response predictor in clear cell renal cell carcinoma via high-throughput CpG Island screening.Clinical epigenetics · 2025Article
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Classification of acute myeloid leukemia based on multi-omics and prognosis prediction value.Molecular oncology · 2025Article
- Enhanced efficacy of ipilimumab plus nivolumab in angiogenic subtypes of metastatic clear-cell renal cell carcinoma.NPJ precision oncology · 2025Article
- Simulation-guided pan-cancer analysis identifies a novel regulator of CpG island hypermethylation heterogeneity.Briefings in bioinformatics · 2025Article
- Stratification system with dual human endogenous retroviruses for predicting immunotherapy efficacy in metastatic clear-cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Integrated RNA sequencing analysis and machine learning identifies a metabolism-related prognostic signature in clear cell renal cell carcinoma.Scientific reports · 2025Article
- Tertiary lymphoid structures in renal cell carcinoma: from heterogeneity dissection to translational precision immunotherapy.Frontiers in immunology · 2025Review
- Pan-Cancer Analysis of KANK2: Clinical and Molecular Insights into Tumor Progression and Therapeutic Implications.Journal of Cancer · 2025Article
- High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients.Journal of translational medicine · 2024Article
- NEDD4L Suppresses Proliferation and Promotes Apoptosis by Ubiquitinating RAC2 Expression and Acts as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial. High iMES is associated with VEGF pathway silencing, endothelial cell depletion, immune activation/suppression, EZH2 activation, BAP1/SETD2 deficiency, and resistance to ICI. Combination therapy with hypomethylating agents or tyrosine kinase inhibitors may benefit patients with high iMES. Intriguingly, tumors with low iMES exhibit increased endothelial cells and improved ICI response, suggesting the importance of angiogenesis in ICI treatment. We also develop a transcriptome-based analogous system for extended applicability of iMES. Our study underscores the interplay between epigenetic alterations and tumor microenvironment in determining immunotherapy response.
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