PXD070440-1

PXD070440 is an original dataset announced via ProteomeXchange.

Title	THBS1 as a Candidate Biomarker and Fibrotic Mediator in Radiation-induced liver injury: Insights from TMT-Labeled Quantitative Proteomics
Description	Objective: Radiation-induced liver injury (RILI) is one of the most dreaded complications in radiotherapy for hepatocellular carcinoma (HCC), causing serious impact on the course of treatment and the survival quality of patients. This study was conducted to screen effective biomarkers for the diagnosis and disease course monitoring of RILI. Methods: This study established a rat model of RILI, with the assessment of liver injury by hematoxylin-eosin (HE) staining. High-throughput screening of RILI and normal liver tissue samples was performed using TMT quantitative proteomics technology, followed by the analysis of differentially expressed proteins (DEPs) using GO and KEGG. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were further employed to identify THBS1 as a key protein of RILI. We knocked down THBS1 in rat (BRL, BRL-3A) and human (THLE-2) hepatocytes using siRNA and applied Ruxolitinib to inhibit the JAK2/STAT3 pathway, further clarifying the role of THBS1 in this signaling process. Validation was performed by protein-protein docking and western blot. The concentration of THBS1 in plasma was determined using enzyme linked immunosorbent assay (ELISA), while the consistency of plasma and tissue expression was analyzed by Pearson's correlation analysis. Results: Proteomic analysis identified 176 DEPs, of which 106 were up-regulated, with THBS1 identified as a key protein highly expressed in RILI. THBS1 could activate the PDGFA/PDGFR signaling pathway and further activation of the JAK2/STAT3 pathway. Result in the deposition of COL5A and COL6A. Silencing THBS1 with siRNA in BRL, BRL-3A, and THLE-2 cells significantly reversed the activation of the JAK2/STAT3 signaling pathway and the overexpression of collagens in the cellular models. In addition, plasma ELISA revealed that the concentration of THBS1 in plasma increased with increasing radiation dose and degree of RILI, which was consistent with the expression level in the liver tissue. Conclusion: This study provides new insights into the pathogenesis of RILI, and identifies THBS1 as a potential biomarker for RILI diagnosis and monitoring.
HostingRepository	iProX
AnnounceDate	2025-11-06
AnnouncementXML	Submission_2025-11-06_23:28:01.419.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zixi Wang
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-06 23:27:47	ID requested
⏵ 1	2025-11-06 23:28:01	announced

Dataset with its publication pending

submitter keyword: Proteomics, TMT, JAK2/STAT3, THBS1, biomarkers

Ying Yan
contact affiliation	General Hospital of Northern Theater Command
contact email	yanyingdoctor@sina.com
lab head
Zixi Wang
contact affiliation	General Hospital of Northern Theater Command
contact email	wongzzzx@163.com
dataset submitter

iProX dataset URI