PuSH - Publication Server of Helmholtz Zentrum München: Analyses of molecular subtypes and their association to mechanisms ofradioresistance in patients with HPV-negative HNSCC treated bypostoperative radiochemotherapy.

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Patil, S.* ; Tawk, B.* ; Grosser, M.* ; Lohaus, F.* ; Gudziol, V.* ; Kemper, M.* ; Nowak, A.* ; Haim, D.* ; Tinhofer, I.* ; Budach, V.* ; 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.* ; Zips, D.* ; Baretton, G.B.* ; Baumann, M.* ; Krause, M.* ; Löck, S.* ; Linge, A.*

Analyses of molecular subtypes and their association to mechanisms ofradioresistance in patients with HPV-negative HNSCC treated bypostoperative radiochemotherapy.

Radiother. Oncol. 167, 300-307 (2022)

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Open Access Green as soon as Postprint is submitted to ZB.

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PURPOSE: To assess the relation of the previously reported classification of molecular subtypes to the outcome of patients with HNSCC treated with postoperative radio(chemo)therapy (PORT-C), and to assess the association of these subtypes with gene expressions reflecting known mechanisms of radioresistance. MATERIAL AND METHODS: Gene expression analyses were performed using the GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective patient cohort (N=128) of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) with locally advanced HNSCC treated with PORT-C. Tumours were assigned to four molecular subtypes, and correlation analyses between subtypes and clinical risk factors were performed. In addition, the classifications of eight genes or gene signatures related to mechanisms of radioresistance, which have previously shown an association with outcome of patients with HNSCC, were compared between the molecular subtypes. The endpoints loco-regional control (LRC) and overall survival (OS) were evaluated by log-rank tests and Cox regression. RESULTS: Tumours were classified into the four subtypes basal (19.5%), mesenchymal (18.8%), atypical (15.6%) and classical (14.1%). The remaining tumours could not be classified (32.0%). Tumours of the mesenchymal subtype showed a lower LRC compared to the other subtypes (p=0.012). These tumours were associated with increased epithelial-mesenchymal transition (EMT) and overexpression of a gene signature enriched in DNA repair genes. The majority of the eight considered gene classifiers were significantly associated to LRC or OS in the whole cohort. CONCLUSION: Molecular subtypes, previously identified on HNSCC patients treated with primary radio(chemo)therapy or surgery, were related to LRC for patients treated with PORT-C, where mesenchymal tumour presented with worse prognosis. After prospective validation, subtype-based patient stratification, potentially in combination with other molecular classifiers, may be considered in future interventional studies in the context of personalised radiotherapy and may guide the development of combined treatment approaches.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cancer Stem Cells ; Gene Signatures ; Head And Neck Squamous Cell Carcinoma ; Hypoxia ; Postoperative Radiotherapy ; Primary Radiotherapy

ISSN (print) / ISBN 0167-8140

e-ISSN 1879-0887

Journal Radiotherapy and Oncology

Quellenangaben Volume: 167, Pages: 300-307

Publisher Elsevier

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)