Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy

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 AL, Abdollahi A, Debus J, Ganswindt U, Belka C, Pigorsch S, Combs SE, Moennich D, Zips D, Baretton GB, Buchholz F, Baumann M, Krause M, Loeck S (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Clinical Cancer Research American Association for Cancer Research

Book Volume: 24

Pages Range: 1364-1374

Journal Issue: 6

DOI: 10.1158/1078-0432.CCR-17-2345

Abstract

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.

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Technische Universität Dresden DE Germany (DE)

How to cite

APA:

Schmidt, S., Linge, A., Zwanenburg, A., Leger, S., Lohaus, F., Krenn, C.,... Loeck, S. (2018). Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy. Clinical Cancer Research, 24(6), 1364-1374. https://doi.org/10.1158/1078-0432.CCR-17-2345

MLA:

Schmidt, Stefan, et al. "Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy." Clinical Cancer Research 24.6 (2018): 1364-1374.

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