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Linge, A.* ; Patil, S.* ; Grosser, M.* ; Lohaus, F.* ; Gurtner, K.* ; Kemper, M.* ; Gudziol, V.* ; Haim, D.* ; Nowak, A.* ; Tinhofer, I.* ; Zips, D.* ; Guberina, M.* ; Stuschke, M.* ; Balermpas, P.* ; Rödel, C.* ; Schäfer, H.* ; Grosu, A.L.* ; Abdollahi, A.* ; Debus, J.* ; Ganswindt, U.* ; Belka, C. ; Pigorsch, S.* ; Combs, S.E. ; Boeke, S.* ; Gani, C.* ; Jöhrens, K.* ; Baretton, G.B.* ; Löck, S.* ; Baumann, M.* ; Krause, M.*

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 (2023)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Gene Signature ; Head And Neck Squamous Cell Carcinoma ; Hypoxia ; Molecular Subtypes ; Postoperative Radiochemotherapy ; Radiosensitivity ; Xenograft; Squamous-cell Carcinoma; Good Prognosis Subgroups; Local Tumor-control; Postoperative Radiochemotherapy; Fractionated-irradiation; Expression Classifier; Hypoxic Modification; Marker Expression; Clonogenic Cells; Egfr-inhibition
ISSN (print) / ISBN 0167-8140
e-ISSN 1879-0887
Journal Radiotherapy and Oncology
Quellenangaben Volume: 191, Issue: , Pages: , Article Number: 110055 Supplement: ,
Publisher Elsevier
Publishing Place Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Institute of Radiation Medicine (IRM)
Grants Research Center/German Cancer Consortium