A20 as a Potential New Tool in Predicting Recurrence and Patient's Survival in Oral Squamous Cell Carcinoma

Steffen Spoerl; Ramona Erber; Michael Gerken; Juergen Taxis; Nils Ludwig; Felix Nieberle; Niklas Biermann; Carol Immanuel Geppert; Tobias Ettl; Arndt Hartmann; Philipp Beckhove; Torsten E Reichert; Gerrit Spanier; Silvia Spoerl

doi:10.3390/cancers15030675

A20 as a Potential New Tool in Predicting Recurrence and Patient's Survival in Oral Squamous Cell Carcinoma

Cancers (Basel). 2023 Jan 21;15(3):675. doi: 10.3390/cancers15030675.

Affiliations

¹ Department of Cranio-Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
² Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
³ Tumor Center, Institute for Quality Management and Health Services Research, University of Regensburg, 93053 Regensburg, Germany.
⁴ Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
⁵ Division of Interventional Immunology, Leibniz Institute for Immunotherapy, 93053 Regensburg, Germany.
⁶ Department of Internal Medicine 5-Haematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

Abstract

A20, known as a potent inhibitor of NF-κB signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003-2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan-Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388-0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411-0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC.

Keywords: A20; OSCC; TNFAIP3; oral squamous cell carcinoma; tissue microarray.

Grants and funding

This work received a grant from the Else Kröner-Fresenius-Stiftung, “Else Kröner-Forschungskolleg Regensburg—Interdisziplinäre translationale Immuno-Onkologie”. Some authors were supported by the Interdisciplinary Center for Clinical Research (IZKF, Clinician Scientist Program) of the Medical Faculty of the FAU Erlangen-Nürnberg. Additionally, individual authors were supported by a grant from SFB TRR221 (project B01), Deutsche Forschungsgemeinschaft.