Translational Oral Biosciences Laboratory, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK.
Department of Oral & Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
J Oral Pathol Med. 2023 Sep;52(8):710-717. doi: 10.1111/jop.13460. Epub 2023 Jun 20.
Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers.
Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels.
The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples.
Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.
大多数口腔鳞状细胞癌患者就诊时已处于晚期。因此，早期发现口腔癌被认为是改善患者预后的最有效方法。已经有一些生物标志物被确定为口腔癌发展和进展的指标；然而，这些标志物都尚未转化为临床实践。在这项研究中，我们研究了内吞衔接蛋白 Epsin3 和跨膜信号蛋白 Notch1 在口腔癌发生中的作用，旨在探索它们作为生物标志物的潜力。
使用口腔癌细胞系和正常口腔角质形成细胞系，以及正常口腔黏膜组织样本（n=21）、口腔上皮异型增生组织样本（n=74）和早期口腔鳞状细胞癌组织样本（n=31）进行免疫细胞化学染色、免疫印迹和实时定量聚合酶链反应（PCR），以评估蛋白和基因表达水平。
Epsin3 和 Notch1 的 mRNA 和蛋白表达水平在不同的口腔鳞状细胞癌细胞系中存在差异。与正常上皮相比，Epsin3 在口腔上皮异型增生和口腔鳞状细胞癌组织中上调。Epsin3 的过表达导致口腔鳞状细胞癌中 Notch1 表达显著降低。Notch1 在异型增生和口腔鳞状细胞癌样本中通常下调。
Epsin3 在口腔上皮异型增生和口腔鳞状细胞癌中上调，有望作为口腔上皮异型增生的生物标志物。Notch 信号通路在口腔鳞状细胞癌中下调，可能通过 Epsin3 诱导的失活途径。
