PXD053079-1

PXD053079 is an original dataset announced via ProteomeXchange.

Title	Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma
Description	Background and Aims: Signet-Ring (SR) cell carcinoma (SRCC) is an increasingly prevalent form of gastric cancer, known for its late presentation and poor treatment outcomes. Using our spatial proteomics pipeline, Deep Visual Proteomics (DVP), we aimed to comprehensively explore the SRCC proteome landscape in a single patient to uncover unknown disease mechanisms that could be individually targeted for therapeutic purposes. Methods: We applied DVP, which combines image-based artificial intelligence with automated microdissection and ultra-high sensitivity mass spectrometry, to SR cell-positive tissues from the bladder, seminal vesicle, lymph node, and prostate within a single patient. Results: DVP allowed us to perform in-depth spatial proteome analysis of SRCC presenting in different organs of a single patient. We identified alternations in DNA damage response (DDR) pathways, particularly in the pathways associated with ataxia-telangiectasia mutant (ATR) and DNA mismatch repair (MMR), suggesting replication stress as the leading factor of SRCC mutagenicity. Additionally, we identified an enrichment of immune-related proteins and could observe infiltration of cytotoxic T lymphocytes. Conclusion: Analyzing the SRCC proteome across different organs within a single patient allowed us to confirm known disease patterns and identify novel biological mechanisms contributing to SRCC aggressiveness. Our data provided insights into why chemotherapy was unsuccessful and explained the significant life extension and improved quality of life following PD-1 inhibitor treatment, which led to tumor stasis.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_19:41:26.283.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-13 07:00:10	ID requested
⏵ 1	2025-05-06 19:41:27	announced

Kabatnik S, Zheng X, Pappas G, Steigerwald S, Padula MP, Mann M, Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma. NPJ Precis Oncol, 9(1):37(2025) [pubmed]

10.1038/s41698-025-00819-7;

submitter keyword: Deep Visual Proteomics, Signet Ring Cell Carcinoma, Precision oncology, Spatial Proteomics, Mass Spectrometry, Pathology, Cancer, Case study

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. NNF Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053079
     1. Label: PRIDE project
     2. Name: Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma