PXD061011

PXD061011 is an original dataset announced via ProteomeXchange.

Title	Deep visual multi-omics profiling reveals mechanisms that underly cancer cell differentiation and aggressiveness in clear cell renal cell carcinoma
Description	Clear cell renal cell carcinoma (ccRCC) exhibits significant intra-tumoral heterogeneity (ITH) at both morphological and genetic levels, complicating treatment and contributing to disease progression. Among these, rhabdoid ccRCCs stand out as highly aggressive tumors distinguished by cells with unique morphological features and poor clinical outcomes3. However, the relationship between distinct cellular morphologies, specific molecular alterations, and their impact on tumor behavior remains poorly understood. Unraveling the molecular underpinnings of cells with clinically relevant histological features will be critical for developing more effective treatments targeting key cellular subsets responsible for tumor progression. In this study, we integrated advanced AI-based image analysis with single-cell isolation and multi-omics profiling to dissect the link between clinically relevant morphological and molecular features of ccRCC cells. Using a novel digital pathology workflow, we precisely quantified low-grade, high-grade, and rhabdoid morphologies in ccRCC diagnostic images. By isolating two sets of 1,000 morphologically distinct cells for detailed mRNA and protein expression analyses we uncovered increasing dysregulation of cancer-relevant molecular pathways associating with higher histopathological grades. Rhabdoid ccRCC cells (grade 4) exhibited a distinct molecular profile, including upregulated FOXM1-driven proliferation, disrupted cell-matrix interactions, and enhanced immune evasion pathways. Despite high T-cell infiltration in rhabdoid areas, we identified a rhabdoid cell-specific immunosuppressive network driven by cytokines, IFN-beta, and integrin signaling, likely contributing to T-cell exhaustion. These findings provide a basis for novel combination treatment strategies aimed at enhancing immune checkpoint inhibitor (ICI) efficacy in patients with aggressive rhabdoid ccRCC.
HostingRepository	PRIDE
AnnounceDate	2025-02-21
AnnouncementXML	Submission_2025-02-21_02:32:09.309.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dorothea Rutishauser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-20 10:36:22	ID requested
⏵ 1	2025-02-21 02:32:09	announced

Dataset with its publication pending

submitter keyword: omics, AI-based image analysis, single cell,Renal cell carcinoma (RCC), Laser microdissection

Dorothea Rutishauser
contact affiliation	Department of Pathology and Molecular Pathology, University Hospital Zürich and University of Zürich, Zürich, Switzerland
contact email	dorothea.rutishauser@usz.ch
lab head
Dorothea Rutishauser
contact affiliation	University Hospital Zurich
contact email	dorothea.rutishauser@usz.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/02/PXD061011

PRIDE project URI

• PRIDE
  1. PXD061011
     1. Label: PRIDE project
     2. Name: Deep visual multi-omics profiling reveals mechanisms that underly cancer cell differentiation and aggressiveness in clear cell renal cell carcinoma