Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy
Objective: To validate the impact of HPV status, cancer stem cell (CSC) marker expression and tumour hypoxia status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The results of the exploration cohort have previously been rep...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-12-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405630816300064 |
| _version_ | 1819132015876767744 |
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| author | Annett Linge Steffen Löck Constanze Krenn Steffen Appold Fabian Lohaus Alexander Nowak Volker Gudziol Gustavo B. Baretton Frank Buchholz Michael Baumann Mechthild Krause |
| author_facet | Annett Linge Steffen Löck Constanze Krenn Steffen Appold Fabian Lohaus Alexander Nowak Volker Gudziol Gustavo B. Baretton Frank Buchholz Michael Baumann Mechthild Krause |
| author_sort | Annett Linge |
| collection | DOAJ |
| description | Objective: To validate the impact of HPV status, cancer stem cell (CSC) marker expression and tumour hypoxia status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The results of the exploration cohort have previously been reported by the German Cancer Consortium Radiation Oncology Group (DKTK-ROG; Lohaus et al., 2014; Linge et al., 2016).
Materials and methods: For 152 patients with locally advanced HNSCC the impact of HPV16 DNA status, CSC marker expression and hypoxia-associated gene signatures on outcome of postoperative radiotherapy were retrospectively analysed. Out of them, 40 patients received postoperative radiochemotherapy. Cox models presented in a previous study were validated using the concordance index as a performance measure. The primary endpoint of this study was loco-regional control. Results were compared to those previously reported by DKTK-ROG.
Results: Loco-regional control, freedom from distant metastases and overall survival were inferior to the previously reported cohort. Despite of this, the prognostic value of the combination of HPV infection status, CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in univariate analyses using an independent validation cohort. For multivariate models, the concordance index was between 0.58 and 0.69 in validation, indicating a good prognostic performance of the models. The inclusion of CD44 and the 15-gene hypoxia signature moderately improved the performance compared to a baseline model without CSC markers or hypoxia classifiers.
Conclusions: The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy. |
| first_indexed | 2024-12-22T09:24:41Z |
| format | Article |
| id | doaj.art-c78ce09caaf24412bb55102c0325377e |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-12-22T09:24:41Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-c78ce09caaf24412bb55102c0325377e2022-12-21T18:31:07ZengElsevierClinical and Translational Radiation Oncology2405-63082016-12-011C192610.1016/j.ctro.2016.10.002Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapyAnnett Linge0Steffen Löck1Constanze Krenn2Steffen Appold3Fabian Lohaus4Alexander Nowak5Volker Gudziol6Gustavo B. Baretton7Frank Buchholz8Michael Baumann9Mechthild Krause10German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyOncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, GermanyDepartment of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyNational Center for Tumor Diseases (NCT), Dresden, GermanyNational Center for Tumor Diseases (NCT), Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK), Partner Site Dresden, GermanyObjective: To validate the impact of HPV status, cancer stem cell (CSC) marker expression and tumour hypoxia status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radiotherapy. The results of the exploration cohort have previously been reported by the German Cancer Consortium Radiation Oncology Group (DKTK-ROG; Lohaus et al., 2014; Linge et al., 2016). Materials and methods: For 152 patients with locally advanced HNSCC the impact of HPV16 DNA status, CSC marker expression and hypoxia-associated gene signatures on outcome of postoperative radiotherapy were retrospectively analysed. Out of them, 40 patients received postoperative radiochemotherapy. Cox models presented in a previous study were validated using the concordance index as a performance measure. The primary endpoint of this study was loco-regional control. Results were compared to those previously reported by DKTK-ROG. Results: Loco-regional control, freedom from distant metastases and overall survival were inferior to the previously reported cohort. Despite of this, the prognostic value of the combination of HPV infection status, CSC marker expression (SLC3A2) and tumour hypoxia status could be validated in univariate analyses using an independent validation cohort. For multivariate models, the concordance index was between 0.58 and 0.69 in validation, indicating a good prognostic performance of the models. The inclusion of CD44 and the 15-gene hypoxia signature moderately improved the performance compared to a baseline model without CSC markers or hypoxia classifiers. Conclusions: The HPV status, CSC marker expression of CD44 and SLC3A2 as well as hypoxia status are potential prognostic biomarkers for patients with locally advanced HNSCC treated by postoperative radiotherapy.http://www.sciencedirect.com/science/article/pii/S2405630816300064BiomarkerCancer stem cellsHNSCCHPVHypoxiaPostoperative radiochemotherapyValidation |
| spellingShingle | Annett Linge Steffen Löck Constanze Krenn Steffen Appold Fabian Lohaus Alexander Nowak Volker Gudziol Gustavo B. Baretton Frank Buchholz Michael Baumann Mechthild Krause Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy Clinical and Translational Radiation Oncology Biomarker Cancer stem cells HNSCC HPV Hypoxia Postoperative radiochemotherapy Validation |
| title | Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy |
| title_full | Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy |
| title_fullStr | Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy |
| title_full_unstemmed | Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy |
| title_short | Independent validation of the prognostic value of cancer stem cell marker expression and hypoxia-induced gene expression for patients with locally advanced HNSCC after postoperative radiotherapy |
| title_sort | independent validation of the prognostic value of cancer stem cell marker expression and hypoxia induced gene expression for patients with locally advanced hnscc after postoperative radiotherapy |
| topic | Biomarker Cancer stem cells HNSCC HPV Hypoxia Postoperative radiochemotherapy Validation |
| url | http://www.sciencedirect.com/science/article/pii/S2405630816300064 |
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