PXD016002

PXD016002 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of CSF from patients with leptomeningeal melanoma metastases identifies signatures associated with disease progression and therapeutic resistance
Description	The development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication of the late-stage disease, for which no effective treatments exist. Here, we performed a multi-omics analysis of the CSF from LMM patients to determine how the leptomeningeal microenvironment shapes the biology and therapeutic responses of melanoma cells. A total of 45 serial CSF samples were collected from 16 patients, 8 of these with confirmed LMM. Of those with LMM, 7 had poor survival (<4 months) and one was an extraordinary responder (still alive with survival >32 months). CSF samples were analyzed by mass spectrometry and incubated with melanoma cells, that were subjected to RNA-Seq analysis. Functional assays were performed to validate the pathways identified. Mass spectrometry analyses showed the CSF of most LMM patients to be enriched for pathways involved in innate immunity, protease-mediated damage, and IGF-related signaling. All of these were anti-correlated in the extraordinary responder. RNA-Seq analysis showed CSF to induce PI3K/AKT, integrin, B-cell activation, S-phase entry, TNFR2, TGF- and oxidative stress responses in the melanoma cells. ELISA assays confirmed that TGF- expression increased in the CSF of patients progressing with LMM. CSF from poorly responding patients conferred tolerance to BRAF inhibitor therapy in apoptosis assays. These analyses identified proteomic/transcriptional signatures in the CSF of patients who succumbed to LMM. We further showed that the CSF from LMM patients has the potential to modulate BRAF inhibitor responses and may contribute to drug resistance.
HostingRepository	PRIDE
AnnounceDate	2020-01-17
AnnouncementXML	Submission_2020-01-17_06:05:20.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD016002
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex; Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-24 02:57:53	ID requested
⏵ 1	2020-01-17 06:05:21	announced

Smalley I, Law V, Wyatt C, Evernden B, Fang B, Koomen JM, Welsh EA, Macaulay RJB, Forsyth PA, Smalley KSM, Proteomic Analysis of CSF from Patients with Leptomeningeal Melanoma Metastases Identifies Signatures Associated with Disease Progression and Therapeutic Resistance. Clin Cancer Res, 26(9):2163-2175(2020) [pubmed]

submitter keyword: melanoma, brain metastasis, CSF, Proteomics

Keiran Smalley, PhD
contact affiliation	Moffitt Cancer Center Tampa, FL, USA 33612
contact email	keiran.smalley@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
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/2020/01/PXD016002

PRIDE project URI

• PRIDE
  1. PXD016002
     1. Label: PRIDE project
     2. Name: Proteomic analysis of CSF from patients with leptomeningeal melanoma metastases identifies signatures associated with disease progression and therapeutic resistance