PXD059513

PXD059513 is an original dataset announced via ProteomeXchange.

Title	Proteomic Characterization of MET-Amplified Esophageal Adenocarcinomas Reveals Enrichment of Alternative Splicing- and Androgen Signaling-Related Proteins
Description	Background Esophageal adenocarcinomas (EACs) represent an evolving tumor entity with high mortality rates. MET amplification is a recurrent driver in EACs and is associated with decreased patient survival. However, the response to MET inhibitors is limited. Recent studies have identified several mechanisms that lead to resistance against MET inhibitors in different tumor entities. Nonetheless, a characterization of additional vulnerable targets beyond MET has not been conducted in MET-amplified EACs. Methods In this study, we determined the MET amplification status in a cohort of more than 900 EACs using fluorescence in situ hybridization (FISH) and compared the proteomes of MET-amplified versus non-amplified tumors by mass spectrometry. Results We identified a phenotype, present in almost all MET-amplified tumors, which shows an enrichment of alternative RNA splicing, and androgen receptor signaling proteins, as well as decreased patient survival. Additionally, our analyses revealed a negative correlation between MET expression and patient survival in MET-amplified EACs, indicating biological heterogeneity with clinical relevance despite the presence of MET amplification as the predominant oncogenic driver. Furthermore, quantitative immunohistochemical analysis of the inflammatory tumor microenvironment showed that an increased percentage of M2 macrophages is associated with lower overall survival in MET-amplified EACs. Conclusions Our results provide valuable insights into possible new therapeutic approaches for MET-amplified EACs for further research.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:54:57.307.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-07 07:41:24	ID requested
⏵ 1	2025-05-07 06:54:58	announced

10.1007/s00018-025-05635-7;

Grothey B, Lyu SI, Quaas A, Simon AG, Jung JO, Schr, ö, der W, Bruns CJ, Schiffmann LM, Popp FC, Schmidt T, Knipper K, Proteomic characterization of MET-amplified esophageal adenocarcinomas reveals enrichment of alternative splicing- and androgen signaling-related proteins. Cell Mol Life Sci, 82(1):112(2025) [pubmed]

submitter keyword: Esophageal adenocarcinomas, Tumor microenvironment, MET signaling pathway,Oncology, Proteomics

Alexander Quaas
contact affiliation	Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
contact email	Alexander.quaas@uk-koeln.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059513
     1. Label: PRIDE project
     2. Name: Proteomic Characterization of MET-Amplified Esophageal Adenocarcinomas Reveals Enrichment of Alternative Splicing- and Androgen Signaling-Related Proteins