Low cancer stem cell marker expression and low hypoxia identify good prognosis subgroups in HPV(−) HNSCC after postoperative radiochemotherapy: a multicenter study of the DKTK-ROG
Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). - Experimental Design: Expression...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 11, 2016
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| In: |
Clinical cancer research
Year: 2016, Jahrgang: 22, Heft: 11, Pages: 2639-2649 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-15-1990 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-15-1990 Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/early/2016/02/29/1078-0432.CCR-15-1990 
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| Verfasserangaben: | Annett Linge, Steffen Löck, Volker Gudziol, Alexander Nowak, Fabian Lohaus, Cläre von Neubeck, Martin Jütz, Amir Abdollahi, Jürgen Debus, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Melanie Avlar, Anca-Ligia Grosu, Christine Bayer, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, Stefan Welz, Daniel Zips, Frank Buchholz, Daniela E. Aust, Gustavo B. Baretton, Howard D. Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Michael Baumann, and Mechthild Krause for the DKTK-ROG |
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| 245 | 1 | 0 | |a Low cancer stem cell marker expression and low hypoxia identify good prognosis subgroups in HPV(−) HNSCC after postoperative radiochemotherapy |b a multicenter study of the DKTK-ROG |c Annett Linge, Steffen Löck, Volker Gudziol, Alexander Nowak, Fabian Lohaus, Cläre von Neubeck, Martin Jütz, Amir Abdollahi, Jürgen Debus, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Melanie Avlar, Anca-Ligia Grosu, Christine Bayer, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, Stefan Welz, Daniel Zips, Frank Buchholz, Daniela E. Aust, Gustavo B. Baretton, Howard D. Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Michael Baumann, and Mechthild Krause for the DKTK-ROG |
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| 520 | |a Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). - Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control. - Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup. - Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 1-11. ©2016 AACR. | ||
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