Development and validation of a 6-gene signature for the prognosis of loco-regional control in patients with HPV-negative locally advanced HNSCC treated by postoperative radio(chemo)therapy
| Autor: | Shivaprasad Patil, Annett Linge, Marianne Grosser, Fabian Lohaus, Volker Gudziol, Max Kemper, Alexander Nowak, Dominik Haim, Inge Tinhofer, Volker Budach, Maja Guberina, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Henning Schäfer, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, Simon Boeke, Daniel Zips, Gustavo B. Baretton, Michael Baumann, Mechthild Krause, Steffen Löck |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Squamous Cell Carcinoma of Head and Neck
Cancer stem cells Gene Expression Profiling Papillomavirus Infections Medizin Head and neck squamous cell carcinoma Hematology Chemoradiotherapy Chemoradiotherapy Adjuvant Prognosis Risk Assessment Machine Learning Oncology Peroxidases Head and Neck Neoplasms Surgical Procedures Operative Machine learning Biomarkers Tumor Gene signature Humans Radiology Nuclear Medicine and imaging Hypoxia Retrospective Studies |
| Zdroj: | Radiotherapy and Oncology 171(2022), 91-100 |
| Popis: | Purpose: The aim of this study was to develop and validate a novel gene signature from full-transcriptome data using machine-learning approaches to predict loco-regional control (LRC) of patients with human papilloma virus (HPV)-negative locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radio(chemo)therapy (PORT-C). Materials and methods: Gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective training cohort of 128 patients and an independent validation cohort of 114 patients from the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Genes were filtered based on differential gene expression analyses and Cox regression. The identified gene signature was combined with clinical parameters and with previously identified genes related to stem cells and hypoxia. Technical validation was performed using nanoString technology. Results: We identified a 6-gene signature consisting of four individual genes CAV1, GPX8, IGLV3-25, TGFBI, and one metagene combining the highly correlated genes INHBA and SERPINE1. This signature was prognostic for LRC on the training data (ci = 0.84) and in validation (ci = 0.63) with a significant patient stratification into two risk groups (p = 0.005). Combining the 6-gene signature with the clinical parameters T stage and tumour localisation as well as the cancer stem cell marker CD44 and the 15-gene hypoxia-associated signature improved the validation performance (ci = 0.69, p = 0.001). Conclusion: We have developed and validated a novel prognostic 6-gene signature for LRC of HNSCC patients with HPV-negative tumours treated by PORT-C. After successful prospective validation the signature can be part of clinical trials on the individualization of radiotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|