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PXD027525-1

PXD027525 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma
DescriptionPurpose Antibody-blockade of PD-1 shows durable responses, but so far, few biomarkers accurately predict if patients with metastatic melanoma will respond. Experimental design We analyzed baseline serum samples (n=56) and tumor cell cultures (n=8), from melanoma patients treated with anti-PD1 therapy. Two approaches concentrating low abundant proteins in serum and two different mass spectrometry (MS) methods were applied: depletion of high abundant proteins with shotgun-MS, and N-glycosite enrichment combined with SWATH-MS. Tumor cell cultures were processed as whole cell lysates with subsequent shotgun-MS. Results Focusing on the non-responder proteome, we identified pathways such as inflammatory processes, cell adhesion and migration, scavenger receptor activity, RAGE receptor binding, platelet aggregation, neutrophil degranulation and integrin signaling to be upregulated. Analyzing the tumor cell proteome revealed a distinctive immunophenotype with CD antigens highly overexpressed in non-responders. Validation of a subset of these markers, performed by immunofluorescence staining of a tissue microarray, revealed a higher mean of positive cells in the tumor microenvironment of non-responders. Validation of serum proteome markers on a second baseline cohort by using a timsTOF for ion mobility MS, revealed significant differences between responder and non-responder for the proteins ORM2, SERPINA1, EFEMP1, and VASN. TCGA survival analysis demonstrated prognostic significance for multiple proteins of our signature correlating with lower overall survival in melanoma patients. Based on this study, we suggest a protein-panel for responsiveness to PD-1 blockade consisting of 14 serum and 33 tumor cell markers that will be the basis for further research.
HostingRepositoryPRIDE
AnnounceDate2023-08-18
AnnouncementXMLSubmission_2023-08-18_05:10:34.942.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristopherGerner
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-25 13:53:33ID requested
12023-08-18 05:10:35announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: shotgun-MS,Immunotherapy, Glycoproteomics, predictive biomarker, SWATH-MS, Serumdepletion
Contact List
ChristopherGerner
contact affiliationUniversity of Vienna, Faculty of Chemistry, Joint Metabolome Facility, Department of Analytical Chemistry
contact emailchristopher.gerner@univie.ac.at
lab head
ChristopherGerner
contact affiliationUniversity of Vienna
contact emailchristopher.gerner@univie.ac.at
dataset submitter
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Dataset FTP location
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