PXD046354

PXD046354 is an original dataset announced via ProteomeXchange.

Title	Deep Visual Proteomics and spatial transcriptomics reveal the landscape of tumor malignancy in borderline ovarian cancer
Description	Women of reproductive age can develop serous borderline tumors (SBT) characterized by the uncontrolled growth of epithelial cells that do not invade the stroma. Despite a good prognosis after surgery, SBT may recur as low-grade serous cancer (LGSC), which is invasive and responds poorly to current standard chemotherapy. SBT and LGSC have overlapping genomic changes, but a putative transition sequence is poorly understood. Here, we employ Deep Visual Proteomics (DVP), a recently introduced single cell type specific spatial technology, to elucidate the evolution of this cancer at the molecular level. We show that the transition of SBT to LGSC occurs in the epithelial compartment through an intermediary stage with micropapillary features (SBT-MP) which involves a gradual increase in MAPK signaling. Proteomics identified several neuronal proteins, including the splicing factor NOVA2, that are exclusive to LGSC and its corresponding metastasis. In the stroma we observed major differences between non-invasive and invasive phenotypes. An acute inflammatory response was only found in SBT-MP. Spatial transcriptomics complemented the insights gained from proteomics, showing an increase in c-Met signaling, mRNA splicing in the epithelium, and HIF1α/angiogenesis in stroma between SBT and the more invasive phenotypes. Inhibiting the most prominently regulated pathways validated our results and suggested an FDA-approved FOLR1 inhibitor as a potential therapeutic strategy. Knockdown or inhibition of the top hits identified using spatial proteomics and transcriptomics confirmed their functional significance regulating migration and invasion. Combining spatial proteomics with transcriptomics is a promising approach to gaining mechanistic insights into tumor transformations and identifying novel treatment strategies.
HostingRepository	PRIDE
AnnounceDate	2025-06-20
AnnouncementXML	Submission_2025-06-20_03:08:43.105.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	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-24 06:32:10	ID requested
⏵ 1	2025-06-20 03:08:43	announced

Dataset with its publication pending

submitter keyword: Spatial, Mass Spectrometry, Ovarian Cancer, Pathology, Serous Borderline, Multi-omics, Low-grade serous cancer, Proteomics, Malignancy,DVP, GeoMX

Matthias Mann
contact affiliation	Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
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. PXD046354
     1. Label: PRIDE project
     2. Name: Deep Visual Proteomics and spatial transcriptomics reveal the landscape of tumor malignancy in borderline ovarian cancer