PXD048525

PXD048525 is an original dataset announced via ProteomeXchange.

Title	Predictive modelling of brain metastasis development from cancer and non-invasive biomarker-based risk assessment leveraging DNA methylation signatures
Description	Brain metastases (BM) are the most common and among the most deadly brain tumors. Currently, there are no reliable predictors of BM development from primary cancer, limiting early intervention. Here, we obtained 364 tumor/plasma samples from a large cohort of lung adenocarcinoma (LUAD) and BM patients (N=309), the most common BM source. LUAD DNA methylation signatures were evaluated to build and validate an accurate model predicting BM development from LUAD, which was integrated with clinical factors to provide comprehensive patient-specific BM risk probabilities in a nomogram. Additionally, immune and cell interaction gene sets were differentially methylated at promoters in BM versus paired primary LUAD and had aligning dysregulation in the proteome. Immune cells were differentially abundant in BM versus LUAD. Finally, liquid biomarkers identified from methylated cell-free DNA sequenced in plasma were used to generate and validate accurate classifiers for early BM detection. Overall, LUAD methylomes can be leveraged to predict and non-invasively identify BM with high precision, moving towards improved patient outcomes with personalized treatment.
HostingRepository	PRIDE
AnnounceDate	2025-03-21
AnnouncementXML	Submission_2025-03-20_20:57:31.345.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Moran
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Bruker Daltonics instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-13 20:26:00	ID requested
⏵ 1	2025-03-20 20:57:32	announced

Zuccato JA, Mamatjan Y, Nassiri F, Ajisebutu A, Liu JC, Muazzam A, Singh O, Zhang W, Voisin M, Mirhadi S, Suppiah S, Wybenga-Groot L, Tajik A, Simpson C, Saarela O, Tsao MS, Kislinger T, Aldape KD, Moran MF, Patil V, Zadeh G, Prediction of brain metastasis development with DNA methylation signatures. Nat Med, 31(1):116-125(2025) [pubmed]

10.1038/s41591-024-03286-y;

submitter keyword: Brain metastases,Lung adenocarcinoma, DNA methylation, Proteomics, Biomarkers

Michael F. Moran
contact affiliation	Professor, Department of Molecular Genetics, University of Toronto, Canada Scientific Director, SPARC BioCentre, Hospital for Sick Children (Sickkids), Toronto, Canada
contact email	mmoran@sickkids.ca
lab head
Michael Moran
contact affiliation	The Hospital for sick children
contact email	mmoran@sickkids.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048525
     1. Label: PRIDE project
     2. Name: Predictive modelling of brain metastasis development from cancer and non-invasive biomarker-based risk assessment leveraging DNA methylation signatures