Evidence map›Paper›PMID 40753869›Full record

ArticleNeoplasia (New York, N.Y.)2025

Proteomic characterization of the pseudocapsule of clear cell renal cell carcinoma in VHL disease reveals a distinct microenvironment at the tumor boundary zone.

Tobias Feilen, Manuel Rogg, Grigor Andreev, Niko Pinter, Maximilian Wess, Anna L Kössinger, Nastasja Diel, Elke Neumann-Haefelin, Athina Ganner, Markus Grabbert and 2 more

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Article in Neoplasia (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tobias FeilenInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
Manuel RoggInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Grigor AndreevInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Niko PinterInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Maximilian WessInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
Anna L KössingerInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nastasja DielInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Elke Neumann-HaefelinRenal Division, Department of Medicine, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department II of Internal Medicine, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.
Athina GannerRenal Division, Department of Medicine, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Markus GrabbertDepartment of Urology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Christoph SchellInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Oliver SchillingInstitute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: oliver.schilling@uniklinik-freiburg.de.

Funding

Deutsche Forschungsgemeinschaft
6 · The paper itself

Abstract

Von Hippel-Lindau (VHL) disease describes a hereditary tumor predisposition syndrome, caused by germline mutations in the VHL tumor suppressor gene, resulting in the functional loss of the VHL protein (pVHL). pVHL loss translates into a pseudo-hypoxic state that drives clear cell renal cell carcinoma (ccRCC) development. ccRCC tumors frequently form a pseudocapsule (PC) at the tumor boundary. This study describes the first comprehensive proteomic analysis of the PC in ccRCC patients with hereditary VHL inactivation, revealing a distinctive matrisomal signature. We conducted a deep, mass spectrometry-based proteomic analysis of 130 formalin-fixed paraffin-embedded (FFPE) ccRCC samples, comprising 54 tumor, 45 PC, and 31 non-malignant adjacent tissue (NAT) specimens from 34 patients. The PC exhibited unique matrisomal features, with pronounced enrichment of structural extracellular matrix (ECM) components, ECM processing enzymes, and secreted signaling proteins such as TGFβ2. Its proteome composition, including proteins involved in immune response, varied with tumor size and semi-tryptic peptide analysis indicated selective ECM processing in the PC and elevated levels of proteolysis within the tumor. Further, tumor proteomes reflected canonical VHL-driven metabolic reprogramming, including upregulated glycolysis and hypoxia markers, suppressed aerobic metabolism, and dysregulated fatty acid metabolism. Enriched immunoproteasome, MHC-I, and inflammasome proteins indicated an active immune response. Pro-angiogenic factors enriched in the tumor partially extended into the PC. Comparison of primary vs metachronous ccRCC cases uncovered proteomic tumor plasticity in VHL disease. Together, our study delineates the PC as an active, signaling-rich compartment at the ccRCC boundary with potential implications for tumor progression and clinical relevance beyond a mere structural scaffold.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsNeoplasms, Second PrimaryTumor Microenvironmentvon Hippel-Lindau DiseaseVon Hippel-Lindau Tumor Suppressor ProteinAdultDisease ProgressionFemaleGerm-Line MutationHumansKidneyMaleMiddle AgedProteomicsVHL protein, humanVon Hippel-Lindau Tumor Suppressor ProteinClear cell renal cell carcinomaExtracellular matrixProteomicsPseudocapsuleVon Hippel-Lindau disease

Identifiers

PMID40753869
PMCPMC12446972

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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.