Erschienen in:
01.09.2023 | Research
Radiation-sensitive genetic prognostic model identifies individuals at risk for radiation resistance in head and neck squamous cell carcinoma
verfasst von:
Peimeng You, Shengbo Liu, Qiaxuan Li, Daipeng Xie, Lintong Yao, Chenguang Guo, Zefeng Guo, Ting Wang, Hongrui Qiu, Yangzhong Guo, Junyu Li, Haiyu Zhou
Erschienen in:
Journal of Cancer Research and Clinical Oncology
|
Ausgabe 17/2023
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Abstract
Background
The advantages of radiotherapy for head and neck squamous cell carcinoma (HNSCC) depend on the radiation sensitivity of the patient. Here, we established and verified radiological factor-related gene signature and built a prognostic risk model to predict whether radiotherapy would be beneficial.
Methods
Data from The Cancer Genome Atlas, Gene Expression Omnibus, and RadAtlas databases were subjected to LASSO regression, univariate COX regression, and multivariate COX regression analyses to integrate genomic and clinical information from patients with HNSCC. HNSCC radiation-related prognostic genes were identified, and patients classified into high- and low-risk groups, based on risk scores. Variations in radiation sensitivity according to immunological microenvironment, functional pathways, and immunotherapy response were investigated. Finally, the expression of HNSCC radiation-related genes was verified by qRT-PCR.
Results
We built a clinical risk prediction model comprising a 15-gene signature and used it to divide patients into two groups based on their susceptibility to radiation: radiation-sensitive and radiation-resistant. Overall survival was significantly greater in the radiation-sensitive than the radiation-resistant group. Further, our model was an independent predictor of radiotherapy response, outperforming other clinical parameters, and could be combined with tumor mutational burden, to identify the target population with good predictive value for prognosis at 1, 2, and 3 years. Additionally, the radiation-resistant group was more vulnerable to low levels of immune infiltration, which are significantly associated with DNA damage repair, hypoxia, and cell cycle regulation. Tumor Immune Dysfunction and Exclusion scores also suggested that the resistant group would respond less favorably to immunotherapy.
Conclusions
Our prognostic model based on a radiation-related gene signature has potential for application as a tool for risk stratification of radiation therapy for patients with HNSCC, helping to identify candidates for radiation therapy and overcome radiation resistance.