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Titel:

The value of subcutaneous xenografts for individualised radiotherapy in HNSCC: Robust gene signature correlates with radiotherapy outcome in patients and xenografts.

Dokumenttyp:
Journal Article
Autor(en):
Linge, Annett; Patil, Shivaprasad; Grosser, Marianne; Lohaus, Fabian; Gurtner, Kristin; Kemper, Max; Gudziol, Volker; Haim, Dominik; Nowak, Alexander; Tinhofer, Inge; Zips, Daniel; Guberina, Maja; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Schäfer, Henning; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Boeke, Simon; Gani, Cihan; Jöhrens, Korinna; Baretton, Gustavo B; Löck, Steffen; Baumann, Michael; Krause, Mech...     »
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 AND METHODS: 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). RESULTS: 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). 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.
Zeitschriftentitel:
Radiother Oncol
Jahr:
2024
Band / Volume:
191
Volltext / DOI:
doi:10.1016/j.radonc.2023.110055
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/38109944
Print-ISSN:
0167-8140
TUM Einrichtung:
Klinik und Poliklinik für RadioOnkologie und Strahlentherapie (Prof. Combs)
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