Evidence map›Paper›PMID 41299419›Full record

ArticleBMC cancer2025

MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets.

Karl Knipper, Christiane J Bruns, Felix C Popp, Thomas Schmidt, Bastian Grothey, Alexander Quaas, Su Ir Lyu

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PubMed Full text at PMC Publisher
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Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Karl KnipperFaculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, University of Cologne, Cologne, Germany. karl.knipper@uk-koeln.de.
Christiane J BrunsFaculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, University of Cologne, Cologne, Germany.
Felix C PoppFaculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, University of Cologne, Cologne, Germany.
Thomas SchmidtFaculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Thoracic and Transplantation Surgery, University of Cologne, Cologne, Germany.
Bastian GrotheyFaculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany.
Alexander QuaasFaculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany.
Su Ir LyuFaculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA complete response following neoadjuvant therapy occurs only in a fraction of patients with esophageal adenocarcinoma (EAC). Further targeted treatment options are needed to improve treatment response and patient survival. Mouse double minute 2 homolog (MDM2) is a known oncogene. It is currently under investigation as a potential therapeutic target. However, initial findings have not been groundbreaking. Therefore, this study aimed to identify further potential therapeutic targets in the subtype of MDM2-amplified EAC.

methodsWe screened 656 patients with esophageal adenocarcinoma for their MDM2-amplification status using Fluorescence in situ Hybridization. 57 tumors (8.7%) were MDM2-amplified. The proteome of 35 MDM2-amplified and 37 non-amplified tumors was analyzed using mass spectrometry.

resultsThe comparison of MDM2-amplified and non-amplified tumors revealed various differently expressed proteins and pathways. Hornerin and Bystin were significantly downregulated. Whereas Choline transporter-like protein 2 and Contactin 1 were upregulated in MDM2-amplified EAC. Enrichment analyses revealed that MDM2-amplified EAC showed a more pronounced immunosuppressive phenotype. Furthermore, distinct metabolic pathways like propanoate and tryptophan metabolism were upregulated.

conclusionsSummarizing, we described numerous potential therapeutic targets, suggesting patients with MDM2-amplified tumors could potentially benefit from, exemplary, Mitogen-activated protein kinase kinase inhibitors or tryptophan metabolism inhibitors in new combinational treatment regimens. Future mechanistic studies are needed to validate these findings.

Indexed as

AdenocarcinomaEsophageal NeoplasmsGene Expression Regulation, NeoplasticProto-Oncogene Proteins c-mdm2AgedFemaleGene AmplificationHumansIn Situ Hybridization, FluorescenceMaleMiddle AgedMolecular Targeted TherapyMDM2 protein, humanProto-Oncogene Proteins c-mdm2AmplificationEsophageal adenocarcinomaMDM2Personalized medicinePrognosisProteomics

Identifiers

PMID41299419
PMCPMC12690831

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