Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (6): 1450-1463.doi: 10.12307/2026.573

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Screening of diagnostic markers for endothelial cell Senescence in mice with radiation-induced heart disease and analysis of immune infiltration

Lai Jiaming1, 2, Song Yuling3, Chen Zixi4, Wei Jinghuan5, Cai Hao1, 2, Li Guoquan1, 6   

  1. 1Department of Basic Medical Sciences, Qinghai University Medical College, Xining 810016, Qinghai Province, China; 2Radiation Oncology Department, 3Physical Technology Engineering Department, 4Office of Medical Information, 5Hospital Office, Fifth People’s Hospital/Cancer Hospital of Qinghai Province, Xining 810007, Qinghai Province, China; 6Department of Oncology, Qinghai Provincial People’s Hospital, Xining 810007, Qinghai Province, China
  • Received:2024-11-22 Accepted:2025-01-21 Online:2026-02-28 Published:2025-07-16
  • Contact: Li Guoquan, PhD, Chief physician, Department of Basic Medical Sciences, Qinghai University Medical College, Xining 810016, Qinghai Province, China; Department of Oncology, Qinghai Provincial People’s Hospital, Xining 810007, Qinghai Province, China Co-corresponding author: Cai Hao, PhD, Associate chief physician, Department of Basic Medical Sciences, Qinghai University Medical College, Xining 810016, Qinghai Province, China; Radiation Oncology Department, Fifth People’s Hospital/Cancer Hospital of Qinghai Province, Xining 810007, Qinghai Province, China
  • About author:Lai Jiaming, Master candidate, Department of Basic Medical Sciences, Qinghai University Medical College, Xining 810016, Qinghai Province, China; Radiation Oncology Department, Fifth People’s Hospital/Cancer Hospital of Qinghai Province, Xining 810007, Qinghai Province, China
  • Supported by:
    2019 Qinghai Province “Kunlun Talents - High-end Innovation and Entrepreneurial Talents” Project for Directly Introducing Leading Talents, No. QHKLYC-GDCXCY-2019-026 (to LGQ); Qinghai Provincial Health and Wellness Commission Guiding Subject, No. 2021-wjzdx-79 (to CH); Qinghai Provincial Health and Wellness Commission Guiding Project, No. J2024013 (to CH)

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 quanTIseq 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.

Key words: radiation-induced heart disease, cellular senescence, CCND1, machine learning, diagnostic biomarkers, immune infiltration, weighted gene co-expression network analysis (WGCNA)

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