Fanourakis Galinos, Kyrodimos Efthymios, Papanikolaou Vasileios, Chrysovergis Aristeidis, Kafiri Georgia, Papanikolaou Nikolaos, Verykokakis Mihalis, Tosios Konstantinos, Vastardis Heleni
Department of Oral Biology, School of Dentistry, National and Kapodistrian University of Athens, 2 Thivon Str., 11527 Athens, Greece.
1st ENT Department, Hippokration Hospital, School of Medicine, National and Kapodistrian University of Athens, 114 Vasilissis Sophias Ave., 11527 Athens, Greece.
Diagnostics (Basel). 2023 Feb 3;13(3):569. doi: 10.3390/diagnostics13030569.
The enzymatic activity of APOBEC3B (A3B) has been implicated as a prime source of mutagenesis in head and neck squamous cell carcinoma (HNSCC). The expression of Protein Kinase C α (PKCα) and Nuclear Factor-κΒ p65 (NF-κΒ p65) has been linked to the activation of the classical and the non-canonical NF-κB signaling pathways, respectively, both of which have been shown to lead to the upregulation of A3B. Accordingly, the aim of the present study was to evaluate the expression of PKCα, NF-κΒ p65 and A3B in non-HPV related oral and oropharyngeal squamous cell carcinomas (SCC), by means of immunohistochemistry and in silico methods. PKCα was expressed in 29/36 (80%) cases of oral and oropharyngeal SCCs, with 25 (69%) cases showing a PKCα+/A3B+ phenotype and only 6/36 (17%) cases showing a PKCα-/A3B+ phenotype. Εxpression of NF-κB p65 was seen in 33/35 (94%) cases of oral and oropharyngeal SCCs, with 30/35 (86%) cases showing an NF-κB p65+/A3B+ phenotype and only 2/35 (6%) cases showing an NF-κB p65-/A3B+ phenotype. In addition, mRNA expression analysis, using the UALCAN database, revealed strong expression of all three genes. These findings indicate that the expression of A3B is associated with PKCα/NF-κB p65 expression and suggest a potential role for the PKC/NF-κB signaling pathway in the development of oral and oropharyngeal cancer.
载脂蛋白B编辑酶催化多肽样蛋白3B（APOBEC3B，A3B）的酶活性被认为是头颈部鳞状细胞癌（HNSCC）诱变的主要来源。蛋白激酶Cα（PKCα）和核因子κB p65（NF-κB p65）的表达分别与经典和非经典NF-κB信号通路的激活有关，这两条信号通路均已被证明可导致A3B上调。因此，本研究的目的是通过免疫组织化学和计算机分析方法，评估PKCα、NF-κB p65和A3B在非HPV相关口腔和口咽鳞状细胞癌（SCC）中的表达。PKCα在29/36（80%）例口腔和口咽SCC中表达，其中25例（69%）表现为PKCα+/A3B+表型，仅6/36（17%）例表现为PKCα-/A3B+表型。在33/35（94%）例口腔和口咽SCC中可见NF-κB p65表达，其中30/35（86%）例表现为NF-κB p65+/A3B+表型，仅2/35（6%）例表现为NF-κB p65-/A3B+表型。此外，使用UALCAN数据库进行的mRNA表达分析显示这三个基因均有强表达。这些发现表明A3B的表达与PKCα/NF-κB p65表达相关，并提示PKC/NF-κB信号通路在口腔和口咽癌发生中可能发挥作用。
