PXD004624

PXD004624 is an original dataset announced via ProteomeXchange.

Title	Multi-omics analysis of serum samples demonstrates reprogramming of organ functions via systemic calcium mobilization and platelet activation in metastatic melanoma patients – proteins from serum samples of melanoma patients with high tumor load
Description	Pathophysiology of cancer-associated syndroms such as cachexia is poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting on nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44 and CO4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics. Remarkably, these molecules are known to be involved in key processes of cancer cachexia. Based on these results, we propose a model how metastatic melanoma may lead to reprogramming of organ functions via formation of platelet activating factors from long-chain polyunsaturated phosphatidylcholines under oxidative conditions and via systemic induction of intracellular calcium mobilization. Calcium mobilization in platelets was demonstrated to regulate several of these marker molecules. Additionally, platelets from melanoma patients proved to be in a rather exhausted state, and platelet-derived eicosanoids implicated in tumor growth were found massively increased in blood from three melanoma patients. Platelets were thus identified as important source of serum protein and lipid alterations in late stage melanoma patients. As a result, the proposed model describes the crosstalk between lipolysis of fat tissue and muscle wasting mediated by oxidative stress, resulting in the metabolic deregulations characteristic for cachexia.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_03:15:33.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD004624
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	residues isobaric at 128.058578 Da; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-21 01:58:34	ID requested
1	2016-12-22 04:30:16	announced
⏵ 2	2017-10-24 03:15:35	announced	Updated project metadata.

Muqaku B, Eisinger M, Meier SM, Tahir A, Pukrop T, Haferkamp S, Slany A, Reichle A, Gerner C, Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma. Mol Cell Proteomics, 16(1):86-99(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Metastatic melanoma, serum analysis, cachexia, damage signature, calcium mobilization, platelet activation, mass spectrometry, shotgun proteomics

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004624
     1. Label: PRIDE project
     2. Name: Multi-omics analysis of serum samples demonstrates reprogramming of organ functions via systemic calcium mobilization and platelet activation in metastatic melanoma patients – proteins from serum samples of melanoma patients with high tumor load