PXD005710

PXD005710 is an original dataset announced via ProteomeXchange.

Title	Proteome Profiling of Renal Cancer Tumor Tissue and Non-Affected Renal Tissue in Patients with Von Hippel-Lindau Disease Highlights Differential Regulation of Xaa-Pro Aminopeptidases-1 and -2 (XPNPEP-1 and -2)
Description	Patients with loss-of-function mutations of the von Hippel Lindau gene (“VHL-patients”) often develop clear cell renal cell carcinoma (ccRCC). Using archived, formalin-fixed, paraffin-embedded (FFPE) samples and a cohort of eight cases, we sought to determine global proteome alterations that distinguish ccRCC tissue from adjacent, non-malignant kidney tissue in VHL-patients. Our quantitative proteomic analysis clearly discriminated tumor and non-malignant tissue, yielding comparable proteome profiles for the eight ccRCC cases. Limma statistics was used to identify significantly dysregulated proteins in ccRCC. Functional classification of these proteins highlighted a decrease in proteins involved in the tricarboxylic acid cycle and an increase in proteins involved in glycolysis. This profile possibly represents a proteomic fingerprint of the “Warburg effect”, which is a molecular hallmark of ccRCC. Furthermore, we observed an increase in proteins involved in extracellular matrix organization. Of particular note were opposing alterations of Xaa-Pro Aminopeptidases-1 and -2 (XPNPEP-1 and -2): a strong decrease of XPNPEP-2 in ccRCC was accompanied by a strong increase of the related protease XPNPEP-1. In both cases, we corroborated the proteomic results by immunohistochemical analysis of ccRCC and adjacent, non-malignant kidney tissue of VHL patients. To functionally investigate the role of XPNPEP-1 in ccRCC, we performed small-hairpin RNA mediated XPNPEP-1 expression silencing in 786-O ccRCC cells harboring a mutated VHL gene. We found that XPNPEP-1 expression suppresses cellular proliferation and migration. These results suggest that XPNPEP-1 is rather an anti-target in VHL-driven ccRCC. Generally, we present one of the first proteomic profiling studies of ccRCC in VHL patients, comparing normal and tumor tissue, which are both deficient for the VHL tumor suppressor. Methodologically, our work further validates the robustness of using FFPE material for quantitative proteomics.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:34:43.349.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Schilling
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-16 02:21:44	ID requested
1	2017-08-28 03:49:56	announced
⏵ 2	2024-10-22 04:34:44	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: von-Hippel-Lindau, exoproteases

Oliver Schilling
contact affiliation	Institute of Molecular Medicine and Cell Research; University of Freiburg, Germany
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Oliver Schilling
contact affiliation	University of Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005710
     1. Label: PRIDE project
     2. Name: Proteome Profiling of Renal Cancer Tumor Tissue and Non-Affected Renal Tissue in Patients with Von Hippel-Lindau Disease Highlights Differential Regulation of Xaa-Pro Aminopeptidases-1 and -2 (XPNPEP-1 and -2)