PXD045328-2

PXD045328 is an original dataset announced via ProteomeXchange.

Title	Characterizing the secretome of EGFR mutant lung adenocarcinoma
Description	Lung cancer is the leading cause of cancer related death worldwide, mainly due to the late stage of disease at the time of diagnosis. Non-invasive biomarkers are needed to supplement existing screening methods to enable earlier detection and increased patient survival. This is critical to EGFR-driven lung adenocarcinoma as it commonly occurs in individuals who have never smoked and do not qualify for current screening protocols. Methods: In this study, we performed mass spectrometry analysis of the secretome of cultured lung cells representing different stages of mutant EGFR driven transformation, from normal to fully malignant. Identified secreted proteins specific to the malignant state were validated using orthogonal methods and their clinical activity assessed in lung adenocarcinoma patient cohorts. Results: We quantified 1020 secreted proteins, which were compared for differential expression between stages of transformation. We validated differentially expressed proteins at the transcriptional level in clinical tumor specimens, association with patient survival, and absolute concentration to yield three biomarker candidates: MDK, GDF15, and SPINT2. These candidates were validated using ELISA and increased levels were associated with poor patient survival specifically in EGFR mutant lung adenocarcinoma patients. Conclusions: Our study provides insight into changes in secreted proteins during EGFR driven lung adenocarcinoma transformation that may play a role in the processes that promote tumor progression. The specific candidates identified can harnessed for biomarker use to identify high risk individuals for early detection screening programs and disease management for this molecular subgroup of lung adenocarcinoma patients.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:19:09.483.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gian Luca Negri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-12 14:29:30	ID requested
1	2024-01-03 13:13:38	announced
⏵ 2	2024-10-22 06:19:09	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: lung adenocarcinoma,Secretome

Gregg Morin
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gmorin@bcgsc.ca
lab head
Gian Luca Negri
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gnegri@bcgsc.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045328
     1. Label: PRIDE project
     2. Name: Characterizing the secretome of EGFR mutant lung adenocarcinoma