2. Academic Validation
  3. Radiotherapy-Associated Cellular Senescence and EMT Alterations Contribute to Distinct Disease Relapse Patterns in Locally Advanced Cervical Cancer

Radiotherapy-Associated Cellular Senescence and EMT Alterations Contribute to Distinct Disease Relapse Patterns in Locally Advanced Cervical Cancer

  • Adv Sci (Weinh). 2025 Feb 4:e2412574. doi: 10.1002/advs.202412574.
Lei Zhang 1,  Jun Ma 2,  Jun Zhang 3 4,  Minjie Hu 5,  Jinlin Cheng 6,  Bin Hu 1,  Junjun Zhou 1,  Di Zhou 1,  Yongrui Bai 1,  Xiumei Ma 1,  Jianming Tang 5,  Haiyan Chen 1,  Ying Jing 3 4
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 2 Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.
  • 3 Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, Guangzhou, 511400, China.
  • 4 State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, 200438, China.
  • 5 Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000, China.
  • 6 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
PMID: 39903771 DOI: 10.1002/advs.202412574
Abstract

A notable number of locally advanced cervical carcinoma (LACC) patients experience local or distant disease relapse following radiotherapy. The contribution of tumor microenvironment (TME) to tumor recurrence at different sites remains unclear. Here, single-nucleus RNA Sequencing data from 28 pre- and on-treatment LACC samples from patients with different disease relapse patterns is analyzed. The findings revealed opposing alterations in the expression levels of the cellular senescence pathway after radiotherapy in patients with local and distant relapses. In contrast, an increase in the expression of the epithelial-mesenchymal transition module after radiotherapy in both relapse groups is observed. Cell-cell interactions, drug-target expression analyses in malignant cells after radiation, and multiplex immunofluorescence of tumor tissue identified interleukin-1 receptor type I (IL1R1) as a potential therapeutic target. It is demonstrated that combining the IL1R1 inhibitor anakinra with radiation can mitigate the effects of radiation on tumor cells. This study highlights the distinct roles of cellular senescence and EMT in tumor recurrence.

Keywords

cellular senescence; cervical squamous carcinoma; disease relapse pattern; epithelial‐mesenchymal transition; radiotherapy; single‐nucleus RNA sequencing.

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