PXD007592-1

PXD007592 is an original dataset announced via ProteomeXchange.

Title	Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases
Description	Background MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but also development of drug resistance within a median progression-free survival (PFS) of 9 to 12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods Cerebral metastases from melanoma patients were prepared for MS analysis by tryptic digestion. Mass spectrometric analysis was performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer, equipped with a nanospray ion source, coupled with a nano HPLC system. Results In this pilot study, we were able to identify 5,977 proteins by LC-MS analysis. Samples were classified into good and poor responders based on PFS. By evaluating these proteomic profiles according to gene ontology (GO) terms, KEGG pathways and gene set enrichment analysis (GSEA), we could characterize differences between the two distinct groups. We further detected an EMT signature, V-type proton ATPases, calcium ion binding proteins, eukaryotic translation initiation factors, cell adhesion proteins and several transporter and exchanger proteins to be significantly up-regulated in poor responding patients, whereas good responders showed an immune-activation and involvement of extracellular matrix structural constituents, among other features. Subsequently we identified the most class-discriminating proteins based on nearest shrunken centroids. Conclusions Using proteomics helped to identify already known extra-cerebral resistance mechanisms in the cerebral metastases and further discovered possible brain specific mechanisms of drug efflux, which might serve as interesting targets, especially for treatment of these types of metastases or as predictive marker.
HostingRepository	PRIDE
AnnounceDate	2018-03-16
AnnouncementXML	Submission_2018-03-16_02:41:14.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD007592
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; L-proline residue; Carbamidomethyl
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-29 23:40:20	ID requested
⏵ 1	2018-03-16 02:41:15	announced
2	2021-01-15 00:17:09	announced	2021-01-15: Updated publication reference for PubMed record(s): 33420112, 29541007.
3	2024-10-22 04:01:40	announced	2024-10-22: Updated project metadata.

Zila N, Bileck A, Muqaku B, Janker L, Eichhoff OM, Cheng PF, Dummer R, Levesque MP, Gerner C, Paulitschke V, Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases. Clin Proteomics, 15():13(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: BRAF mutation, Cerebral melanoma metastases, Drug resistance, Melanoma, MAP kinase inhibitor, 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

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/2018/03/PXD007592

PRIDE project URI

• PRIDE
  1. PXD007592
     1. Label: PRIDE project
     2. Name: Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases