PXD040398-1

PXD040398 is an original dataset announced via ProteomeXchange.

Title	Towards unravelling biological mechanisms behind radiation-induced oral mucositis via mass spectrometry-based proteomics
Description	Objective: Head and neck cancer (HNC) accounts for almost 850,000 new cases per year. Radiotherapy (RT) is used to treat the majority of these patients. A common side-effect of RT-treatment is onset of oral mucositis: a painful irritation and swelling in mouth, which decreases the quality of life and is the major dose-limiting factor in RT. To understand the origin of oral mucositis, the biological mechanisms post-ionizing radiation (IR) need to be understood. This knowledge can be used to develop new treatment targets for oral mucositis and markers for the early identification of “at risk” patients. Results: Mass spectrometry-based proteomics identified 5879 proteins in primary keratinocytes and 4597 proteins in OKF6 cells. Amongst them, 212 proteins in primary keratinocytes and 169 proteins in OKF6 cells were significantly differentially abundant 96 h after 6 Gy irradiation compared to sham-irradiated controls. Protein-protein in silico enrichment predicted interferon (IFN) response and DNA strand elongation pathways as mostly affected pathways in both cell systems. Both pathways were confirmed in OKF6 cells. Immunoblot validations showed a decrease in minichromosome maintenance (MCM) complex proteins 2-7 and an increase in IFN associated proteins STAT1 and ISG15. In line with affected IFN signalling, mRNA levels of IFNβ and interleukin 6 (IL-6) increased significantly following irradiation and also levels of secreted IL-1β IL-6, IP-10, and ISG15 were elevated. Conclusion: This study has investigated biological mechanisms in keratinocytes post-in vitro ionizing radiation. A common radiation signature in keratinocytes was identified. A role of IFN response in keratinocytes along with increased levels of pro-inflammatory cytokines and proteins could hint towards a possible mechanism for oral mucositis.
HostingRepository	PRIDE
AnnounceDate	2023-06-09
AnnouncementXML	Submission_2023-06-09_07:59:18.047.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	StefanieHauck
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-26 08:40:58	ID requested
⏵ 1	2023-06-09 07:59:18	announced
2	2024-10-22 05:47:33	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: keratinocytes, interferon response, STAT phosphorylation,radiotherapy, mass spectrometry-based proteomics, biomarker, MCM complex

StefanieHauck
contact affiliation	Metabolomics and Proteomics Core, Helmholtz zentrum Muenchen
contact email	hauck@helmholtz-muenchen.de
lab head
StefanieHauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040398
     1. Label: PRIDE project
     2. Name: Towards unravelling biological mechanisms behind radiation-induced oral mucositis via mass spectrometry-based proteomics