PXD017149

PXD017149 is an original dataset announced via ProteomeXchange.

Title	Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy
Description	Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a workflow integrating different -omics technologies to identify ccRCC-specific HLA-presented peptides as potential drug targets for ccRCC immunotherapy. We analyzed frequent ccRCC-specific peptides by MS-based HLA ligandomics of 55 ccRCC tumors (cohort 1), paired non-tumor renal tissues and 158 benign tissues from other organs. Pathways enriched in ccRCC compared to its cell type of origin were identified by transcriptome and gene set enrichment analyses in 51 tumor tissues of the same cohort. To retrieve a list of candidate target genes with involvement in ccRCC pathogenesis, ccRCC-specific pathway genes were intersected with the source genes of tumor-exclusive peptides. The candidates were validated in an independent cohort from the Cancer Genome Atlas (TCGA KIRC, n=452), yielding 113 candidate genes. DNA methylation (TCGA KIRC, n=273), and somatic mutations (TCGA KIRC, n=392), as well as correlations with tumor metabolites (cohort 1, n=30) and immune-oncological markers (cohort 1, n=37) were analyzed to refine regulatory and functional involvements of candidates. Immunogenicity analysis identified candidate epitopes able to activate native CD8+ T cells. Functional analysis of EGLN3, a candidate with frequent ccRCC-specific immunogenic peptides, revealed possible tumor-promoting functions. Integration of HLA ligandomics, transcriptomics, genetic and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is now mandatory to expand the treatment landscape of ccRCC.
HostingRepository	PRIDE
AnnounceDate	2020-04-03
AnnouncementXML	Submission_2020-04-03_00:17:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Annika Nelde
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-16 04:44:53	ID requested
⏵ 1	2020-04-03 00:17:43	announced

Reustle A, Di Marco M, Meyerhoff C, Nelde A, Walz JS, Winter S, Kandabarau S, B, ü, ttner F, Haag M, Backert L, Kowalewski DJ, Rausch S, Hennenlotter J, St, ü, hler V, Scharpf M, Fend F, Stenzl A, Rammensee HG, Bedke J, Stevanovi, ć S, Schwab M, Schaeffeler E, Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy. Genome Med, 12(1):32(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: ccRCC, renal cell carcinoma, ligandomics, HLA peptidomie, immunotherapy, peptide vaccine, cancer vaccine, kidney cancer

Stefan Stevanović
contact affiliation	Department of Immunology, Interfaculty Institute for Cell Biology, Tübingen, Germany
contact email	stefan.stevanovic@uni-tuebingen.de
lab head
Annika Nelde
contact affiliation	Department of Hematology and Oncology, University of Tübingen, Germany and Institute for Cell Biology, Department of Immunology, University of Tübingen, Germany
contact email	annika.nelde@uni-tuebingen.de
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/2020/04/PXD017149

PRIDE project URI

• PRIDE
  1. PXD017149
     1. Label: PRIDE project
     2. Name: Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy