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| Verfasst von: | Burkart, Sebastian [VerfasserIn]  |
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| | Weusthof, Christopher [VerfasserIn] |
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| | Khorani, Karam [VerfasserIn] |
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| | Steen, Sonja [VerfasserIn] |
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| | Stögbauer, Fabian [VerfasserIn] |
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| | Unger, Kristian [VerfasserIn] |
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| | Hess, Julia [VerfasserIn] |
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| | Zitzelsberger, Horst [VerfasserIn] |
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| | Belka, Claus [VerfasserIn] |
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| | Kurth, Ina [VerfasserIn] |
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| | Heß, Jochen [VerfasserIn] |
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| Titel: | A novel subgroup of UCHL1-related cancers is associated with genomic instability and sensitivity to DNA-damaging treatment |
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| Verf.angabe: | Sebastian Burkart, Christopher Weusthof, Karam Khorani, Sonja Steen, Fabian Stögbauer, Kristian Unger, Julia Hess, Horst Zitzelsberger, Claus Belka, Ina Kurth and Jochen Hess |
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| E-Jahr: | 2023 |
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| Jahr: | 8 March 2023 |
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| Umfang: | 16 S. |
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| Fussnoten: | Gesehen am 24.04.2023 |
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| Titel Quelle: | Enthalten in: Cancers |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 15(2023), 6 vom: März, Artikel-ID 1655, Seite 1-16 |
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| ISSN Quelle: | 2072-6694 |
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| Abstract: | Purpose: Identification of molecularly-defined cancer subgroups and targeting tumor-specific vulnerabilities have a strong potential to improve treatment response and patient outcomes but remain an unmet challenge of high clinical relevance, especially in head and neck squamous cell carcinoma (HNSC). Experimental design: We established a UCHL1-related gene set to identify and molecularly characterize a UCHL1-related subgroup within TCGA-HNSC by integrative analysis of multi-omics data. An extreme gradient boosting model was trained on TCGA-HNSC based on GSVA scores for gene sets of the MSigDB to robustly predict UCHL1-related cancers in other solid tumors and cancer cell lines derived thereof. Potential vulnerabilities of UCHL1-related cancer cells were elucidated by an in-silico drug screening approach. Results: We established a 497-gene set, which stratified the TCGA-HNSC cohort into distinct subgroups with a UCHL1-related or other phenotype. UCHL1-related HNSC were characterized by higher frequencies of genomic alterations, which was also evident for UCHL1-related cancers of other solid tumors predicted by the classification model. These data indicated an impaired maintenance of genomic integrity and vulnerability for DNA-damaging treatment, which was supported by a favorable prognosis of UCHL1-related tumors after radiotherapy, and a higher sensitivity of UCHL1-related cancer cells to irradiation or DNA-damaging compounds (e.g., Oxaliplatin). Conclusion: Our study established UCHL1-related cancers as a novel subgroup across most solid tumor entities with a unique molecular phenotype and DNA-damaging treatment as a specific vulnerability, which requires further proof-of-concept in pre-clinical models and future clinical trials. |
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| DOI: | doi:10.3390/cancers15061655 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.3390/cancers15061655 |
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| | Volltext: https://www.mdpi.com/2072-6694/15/6/1655 |
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| | DOI: https://doi.org/10.3390/cancers15061655 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | head and neck squamous cell carcinoma (HNSC |
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| | HNSCC) |
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| | integrative multi-omics analysis |
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| | pan-cancer |
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| | radiotherapy |
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| | ubiquitin C-terminal hydrolase L1 |
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| K10plus-PPN: | 1843420252 |
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| Verknüpfungen: | → Zeitschrift |
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¬A¬ novel subgroup of UCHL1-related cancers is associated with genomic instability and sensitivity to DNA-damaging treatment / Burkart, Sebastian [VerfasserIn]; 8 March 2023 (Online-Ressource)
