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A novel 2-metagene signature to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and are treated with PORT

  • (1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.

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Author:Shivaprasad PatilGND, Annett LingeORCiDGND, Hannah Hiepe, Marianne GrosserORCiD, Fabian LohausORCiDGND, Volker GudziolGND, Max KemperGND, Alexander NowakGND, Dominik HaimGND, Ingeborg TinhoferGND, Volker BudachORCiDGND, Maja GuberinaORCiDGND, Martin StuschkeGND, Panagiotis BalermpasORCiDGND, Jens Müller-von der GrünORCiDGND, Henning Sebastian SchäferORCiDGND, Anca-Ligia GrosuORCiDGND, Amir AbdollahiORCiDGND, Jürgen DebusGND, Ute GanswindtORCiDGND, Claus BelkaGND, Steffi Ulrike PigorschORCiDGND, Stephanie CombsGND, Simon BökeGND, Daniel ZipsGND, Korinna JöhrensGND, Gustavo Bruno BarettonGND, Michael BaumannORCiDGND, Mechthild KrauseORCiDGND, Steffen LöckORCiDGND
URN:urn:nbn:de:hebis:30:3-709183
DOI:https://doi.org/10.3390/cancers14123031
ISSN:2072-6694
Parent Title (English):Cancers
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2022/06/20
Date of first Publication:2022/06/20
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:DKTK-ROG
Release Date:2023/01/17
Tag:gene signature; head and neck squamous cell carcinoma; postoperative radiochemotherapy; postoperative radiotherapy; propensity score matching
Volume:14
Issue:12, art. 303
Article Number:303
Page Number:13
First Page:1
Last Page:13
Note:
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14123031/s1, Figure S1: Loco–regional tumour control (A), overall survival (B) and freedom from distant metastases (C) on the PORT and PORT-C cohort before propensity score matching; Figure S2: Loco–regional tumour control (A), overall survival (B) and freedom from distant metastases (C) on the PORT and PORT-C cohort after propensity score matching; Figure S3: Patient stratification by the 2-metagene signature for overall survival (OS) in the PORT (A) and the PORT-C cohort (B) and for freedom from distant metastases (DM) in the PORT (C) and the PORT-C cohort (D); Table S1: Univariable Cox regression of loco–regional tumour control for the clinical parameters in the PORT and PORT-C cohorts before propensity score matching.; Table S2: Patient characteristics for the PORT and PORT-C cohorts before propensity score matching; Table S3: Comparison of the clinical parameters between PORT and PORT-C patients in the original sample and in the propensity score matched sample. The standardized mean and the standardized mean difference between the cohorts are shown. Table S4: Multivariable Cox regression of overall survival for the 2-metagene signature and their interaction term with treatment type; Table S5: Multivariable Cox regression of freedom from distant metastases for the 2-metagene signature and their interaction term with treatment type.
Note:
The study was partly funded by the German Cancer Consortium (DKTK). The DKTK is funded as one of the National German Health Centres by the Federal German Ministry of Education and Research (BMBF).
HeBIS-PPN:505385848
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International

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