The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: Robust gene signature correlates with radiotherapy outcome in patients and xenografts.
Radiother Oncol
; 191: 110055, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38109944
ABSTRACT
PURPOSE:
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. MATERIALS ANDMETHODS:
Mice bearing xenografts (nâ¯=â¯59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (nâ¯=â¯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 50â¯% 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).RESULTS:
Tumours of mesenchymal subtype were characterized by a higher TCD50 (xenografts, pâ¯<â¯0.001) and lower LRC (patients, pâ¯<â¯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, pâ¯<â¯0.001) and for patient outcome in independent validation (LRC pâ¯=â¯0.007).CONCLUSION:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Cabeça e Pescoço
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2024
Tipo de documento:
Article