Screening of diagnostic markers for endothelial cell Senescence in mice with radiation-induced heart disease and analysis of immune infiltration
- VernacularTitle:放射性心脏损伤小鼠内皮细胞衰老的诊断标志物筛选及免疫浸润分析
- Author:
Jiaming LAI
1
;
Yuling SONG
;
Zixi CHEN
;
Jinghuan WEI
;
Hao CAI
;
Guoquan LI
Author Information
- Publication Type:Journal Article
- Keywords: radiation-induced heart disease; cellular senescence; CCND1; machine learning; diagnostic biomarkers; immune infiltration; weighted gene co-expression network analysis(WGCNA)
- From: Chinese Journal of Tissue Engineering Research 2026;30(6):1450-1463
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.
