ArticleNature communications2023
Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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44citing papers in PubMed
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Who cites it
44 citing papers in PubMed, 42 citations in OpenAlex.
- Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.Cancer discovery · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- A tailored in vivo CRISPR screen identifies BAP1 as a potent tumor suppressor of sarcoma.JCI insight · 2026Article
- Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes.Cell reports · 2026Article
- A single chromosome 3p break initiates clear cell renal cell carcinoma evolution.bioRxiv : the preprint server for biology · 2026Article
- Tumour-Derived Extracellular Vesicles Reprogramme Tumour-Associated Macrophages Into Immunosuppressive Phenotype via NOD1 Signalling in Clear Cell Renal Cell Carcinoma.Journal of extracellular vesicles · 2026Article
- Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment.Cell reports. Medicine · 2026Article
- Review
- Integrated metabolomics and transcriptomics analysis unveils key metabolic pathways and potential biomarkers in clear cell renal cell carcinoma.Discover oncology · 2026Article
- Dual itaconate delivery systems modulate macrophage Acod1-Hif-1α-glycolysis axis for immunotherapy of bioprosthetic heart valve calcification.Bioactive materials · 2026Article
- Emerging roles for the epigenetic modifiers PBRM1 SETD2 and BAP1 in clear cell renal cell carcinoma pathogenesis and prognosis beyond VHL.Discover oncology · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Single-cell epigenetic profiling reveals a tumor-intrinsic interferon response program in ccRCC tied to poor prognosis andScience advances · 2026Article
- HIF sustain a transcriptional regulatory circuit of EPAS1 expression in renal clear cell carcinoma.Nature communications · 2026Article
- Noninvasive prediction of occult pT3a upstaging in localized ccRCC with radiogenomic insights and prognostic relevance.NPJ precision oncology · 2026Article
- Construction and verification of a prognostic model of neutrophil-related genes in clear cell renal cell carcinoma.Translational andrology and urology · 2026Article
- ITM2B Truncation Promotes Migrasome Formation to Accelerate Renal Cell Carcinoma Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Lessons learned from spatial transcriptomic analyses in clear-cell renal cell carcinoma.Nature reviews. Urology · 2025Review
- FAPNature communications · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
42 authors at 6 institutions in 1 country.
Yige Wu *Oncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Nadezhda V Terekhanova *Oncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Wagma Caravan *Oncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-4082-6723
Nataly Naser Al Deen *Oncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Preet Lal *Oncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Siqi ChenOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Chia-Kuei MoOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Song CaoOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Yize LiOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-1074-281X
Alla KarpovaOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Ruiyang LiuOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Yanyan ZhaoOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Andrew ShinkleOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Ilya StrunilinOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Cody WeimholtDepartment of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Kazuhito SatoOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-0589-7454
Lijun YaoOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Mamatha SerasanambatiOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Xiaolu YangOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-4749-7803
Matthew WyczalkowskiOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-4197-551X
Houxiang ZhuOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Daniel Cui ZhouOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-7834-2778
Reyka G JayasingheOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-2368-4890
Daniel MendezOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Michael C WendlOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
David ClarkDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA.
Chelsea NewtonVan Andel Institutes, Grand Rapids, MI, 49503, USA.
Yijun RuanThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
Melissa A ReimersOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Russell K PachynskiOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Chris KinsingerOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Scott JewellVan Andel Institutes, Grand Rapids, MI, 49503, USA.ORCID http://orcid.org/0000-0001-9469-6261
Daniel W ChanDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA.
Hui ZhangDepartment of Pathology, Johns Hopkins University, Baltimore, MD, 21231, USA.ORCID http://orcid.org/0000-0001-8726-7098
Aadel A ChaudhuriDepartment of Genetics, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-3115-3061
Milan G ChhedaOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0001-8282-9098
Benjamin D HumphreysOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0002-6420-8703
Mehdi MesriOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Henry RodriguezOffice of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, 20892, USA.
James J HsiehOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.ORCID http://orcid.org/0000-0003-3595-0551
Li DingOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA. lding@wustl.edu.ORCID http://orcid.org/0000-0003-1517-2975
Feng ChenOncology Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA. fchen@wustl.edu.ORCID http://orcid.org/0000-0002-2307-7954
James S. McDonnell Foundation · USWashington University in St. Louis · USJohns Hopkins University · USNational Cancer Institute · USVan Andel Institute · USJackson Laboratory · US
Funding
WASHINGTON UNIVERSITY HUMAN TUMOR ATLAS RESEARCH CENTERU2CCA233303 · NCI · WASHINGTON UNIVERSITY · PI DING, LI · 2018 to 2023
$9.7MProteogenomic Data Analysis for Cancer Systems Biology and Clinical TranslationU24CA210972 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DING, LI, FENYO, DAVID · 2016 to 2020
$3.3MPathogenic Variant Discovery Across a Broad Spectrum of Human DiseasesR01HG009711 · NHGRI · WASHINGTON UNIVERSITY · PI CHEN, FENG, DING, LI · 2017 to 2020
$2.2MOHSU Center for Specialized Data Analysis as part of the GDANU24CA210957 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DEMIR, EMEK, SPELLMAN, PAUL T. · 2016 to 2020
$2.2MDeep Discovery and Clinical Interpretation of Germline and Somatic Cancer DriversU24CA211006 · NCI · WASHINGTON UNIVERSITY · PI DING, LI, GOVINDAN, RAMASWAMY · 2016 to 2020
$1.8MNCI NIH HHS U24 CA210957NCI NIH HHS U24 CA210972NCI NIH HHS U24 CA211006NCI NIH HHS U2C CA233303NHGRI NIH HHS R01 HG009711
Abstract
Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis.
Indexed as
Carcinoma, Renal CellKidney NeoplasmsEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansTranscriptomeTumor Suppressor ProteinsTumor Suppressor Proteins
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