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| Home > Publications database > The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: robust gene signature correlates with radiotherapy outcome in patients and xenografts. |
| Journal Article | DKFZ-2023-02767 |
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2024
Elsevier Science
Amsterdam [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.radonc.2023.110055
Abstract: To assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets.Mice bearing xenografts (n=59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n=242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C). Gene expression analysis was conducted using GeneChip Human Transcriptome Arrays. Xenografts were stratified based on their molecular subtypes and previously established gene classifiers. The dose to control 50% of tumours (TCD50) was compared between these groups. Using differential gene expression analyses combining xenograft and patient data, a gene signature was developed to define risk groups for the primary endpoint loco-regional control (LRC).Tumours of mesenchymal subtype were characterized by a higher TCD50 (xenografts, p<0.001) and lower LRC (patients, p<0.001) compared to the other subtypes. Similar to previously published patient data, hypoxia- and radioresistance-related gene signatures were associated with high TCD50 values. A 2-gene signature (FN1, SERPINE1) was developed that was prognostic for TCD50 (xenografts, p<0.001) and for patient outcome in independent validation (LRC: p=0.007).Genetic prognosticators of outcome for patients after PORT-C and subcutaneous xenografts after primary clinically relevant irradiation show similarity. The identified robust 2-gene signature may help to guide patient stratification, after prospective validation. Thus, xenografts remain a valuable resource for translational research towards the development of individualized radiotherapy.
Keyword(s): gene signature ; head and neck squamous cell carcinoma ; hypoxia ; molecular subtypes ; postoperative radiochemotherapy ; radiosensitivity ; xenograft
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