Analyses of molecular subtypes and their association to mechanisms of radioresistance in patients with HPV-negative HNSCC treated by postoperative radiochemotherapy

Autor: Shivaprasad Patil, Bouchra Tawk, Marianne Grosser, Fabian Lohaus, Volker Gudziol, Max Kemper, Alexander Nowak, Dominik Haim, Inge Tinhofer, Volker Budach, Maja Guberina, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Henning Schäfer, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, Simon Boeke, Daniel Zips, Gustavo B. Baretton, Michael Baumann, Mechthild Krause, Steffen Löck, Annett Linge
Rok vydání: 2021
Předmět:
Zdroj: Radiotherapy and Oncology 167(2022), 300-307
ISSN: 1879-0887
Popis: 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 tumours 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.
Databáze: OpenAIRE
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