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Schmidt, S.* ; Linge, A.* ; Zwanenburg, A.* ; Leger, S.* ; Lohaus, F.* ; Krenn, C.* ; Appold, S.* ; Gudziol, V.* ; Nowak, A.* ; von Neubeck, C.* ; Tinhofer, I.* ; Budach, V.* ; Sak, A.* ; Stuschke, M.* ; Balermpas, P.* ; Roedel, C.* ; Bunea, H.* ; Grosu, A.* ; Abdollahi, A.* ; Debus, J.* ; Ganswindt, U. ; Belka, C. ; Pigorsch, S.U.* ; Combs, S.E. ; Moennich, D.* ; Zips, D.* ; Baretton, G.B.* ; Buchholz, F.* ; Baumann, M.* ; Krause, M.* ; Loeck, S.*

Development and validation of a gene signature for patients with head and neck squamous cell carcinomas treated by postoperative radio(chemo)therapy.

Clin. Cancer Res. 24, 1364-1374 (2018)
Verlagsversion Postprint DOI
Open Access Green
Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio (chemo)therapy (PORT-C). Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms. Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1. The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci ¼ 0.82), which was successfully validated (ci ¼ 0.71). The signature showed improved performance compared with clinical parameters alone (ci ¼ 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci ¼ 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P < 0.001). Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Squamous-cell Carcinoma; Group Dktk-rog; Cancer Stem-cells; Good Prognosis Subgroups; Radiation Oncology; Fractionated-irradiation; Marker Expression; Hpv Status; Hypoxia; Multicenter
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Zeitschrift Clinical Cancer Research
Quellenangaben Band: 24, Heft: 6, Seiten: 1364-1374 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (IDC-TMO)
Institute of Radiation Medicine (IRM)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Radiation Sciences
PSP-Element(e) G-521800-001
G-501300-001
DOI 10.1158/1078-0432.CCR-17-2345
WOS ID WOS:000427627400015
Scopus ID 85048083415
Erfassungsdatum 2018-04-13
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