Spoerl Steffen, Erber Ramona, Gerken Michael, Taxis Juergen, Ludwig Nils, Nieberle Felix, Biermann Niklas, Geppert Carol Immanuel, Ettl Tobias, Hartmann Arndt, Beckhove Philipp, Reichert Torsten E, Spanier Gerrit, Spoerl Silvia
Department of Cranio-Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
Cancers (Basel). 2023 Jan 21;15(3):675. doi: 10.3390/cancers15030675.
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 ( = 0.017) and RFS ( = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388-0.873, = 0.009) and RFS (HR 0.605; 95% CI 0.411-0.889, = 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.
A20作为一种有效的核因子-κB(NF-κB)信号通路抑制剂,已在众多临床及临床前研究中得到了详细描述。最近,尤其是在各种恶性疾病中,对A20的预后及治疗相关性进行了研究。然而,在口腔鳞状细胞癌(OSCC)中,A20的特性尚不清楚。我们分析了229例接受手术治疗的OSCC患者(2003 - 2013年)的组织芯片(TMA)。对A20和CD3进行了免疫组织化学(IHC)染色;此外,还进行了标准苏木精-伊红染色。IHC结果与包含临床和病理组织学信息的综合数据集相关联。在肿瘤细胞以及肿瘤浸润淋巴细胞(TILs)中分析了A20表达,并使用单变量和多变量Cox回归分析其与总生存期(OS)和无复发生存期(RFS)的相关性。中位随访时间为10.9年,与黏膜浸润淋巴细胞(MILs)相比,CD3 + TILs中的A20表达显著降低。在Kaplan-Meier分析中,TILs中较高的A20表达与较好的OS(P = 0.017)和RFS(P = 0.020)相关。在多变量生存分析中,A20过表达与改善的OS(HR:0.582;95% CI 0.388 - 0.873,P = 0.009)和RFS(HR 0.605;95% CI 0.41