PXD027525-1

PXD027525 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma
Description	Purpose 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.
HostingRepository	PRIDE
AnnounceDate	2023-08-18
AnnouncementXML	Submission_2023-08-18_05:10:34.942.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ChristopherGerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-25 13:53:33	ID requested
⏵ 1	2023-08-18 05:10:35	announced

Dataset with its publication pending

submitter keyword: shotgun-MS,Immunotherapy, Glycoproteomics, predictive biomarker, SWATH-MS, Serumdepletion

ChristopherGerner
contact affiliation	University of Vienna, Faculty of Chemistry, Joint Metabolome Facility, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
ChristopherGerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027525
     1. Label: PRIDE project
     2. Name: Proteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma