PXD042949-1

PXD042949 is an original dataset announced via ProteomeXchange.

Title	Targeted proteomics quantittation of NRF2 signaling and predictive biomarkers in HNSCC
Description	The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
HostingRepository	PRIDE
AnnounceDate	2023-06-13
AnnouncementXML	Submission_2023-06-13_13:44:13.901.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	NathanWamsleyu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-13 11:28:53	ID requested
⏵ 1	2023-06-13 13:44:14	announced
2	2024-10-22 05:48:04	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MS/MS

BenMajor
contact affiliation	Washington University in St. Louis
contact email	bmajor@wust.edu
lab head
NathanWamsleyu
contact affiliation	Washington University in St. Louis
contact email	wamsleynathan@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042949
     1. Label: PRIDE project
     2. Name: Targeted proteomics quantittation of NRF2 signaling and predictive biomarkers in HNSCC