UWA Dental School, The University of Western Australia, Nedlands, WA 6009, Australia.
Int J Mol Sci. 2024 May 21;25(11):5597. doi: 10.3390/ijms25115597.
Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1-20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia.
中间丝是形成上皮细胞细胞骨架的三种聚合结构之一。在上皮细胞中，这些丝由多种角蛋白蛋白组成。中间丝在角质形成细胞中完成广泛的功能，包括维持细胞结构、细胞生长、细胞增殖、细胞迁移等。鉴于这些功能与致癌过程密切相关，并且过度角化是口腔白斑的典型特征，角蛋白在口腔白斑中的应用尚未得到充分探索。本范围综述旨在概述基于人类组织原始研究的当前知识，关于角蛋白作为口腔白斑病的诊断、预后和预测生物标志物的表达和用途。使用为几个科学数据库（即 PubMed、Scopus、Web of Science 和 OVID）开发的搜索策略后，有 42 篇论文符合纳入和排除标准。通过手动搜索参考文献列表确定了另外一篇文章。纳入的论文发表于 1989 年至 2024 年之间。在 43 项纳入的研究中研究了角蛋白 1-20，评估了它们在口腔白斑病和异型增生病例中的表达。只有五项研究调查了角蛋白与恶性转化相关的预后作用。没有研究评估角蛋白作为诊断辅助或预测工具。证据支持异型增生破坏初级角蛋白的终末分化途径的观点。在分化的上皮异型增生中，明显观察到角蛋白 17 的表达增加和角蛋白 13 的缺失。此外，角蛋白 19 延伸到基底细胞上方与异型增生的演变特征有关。角蛋白 1/角蛋白 10 的丢失与高级别异型增生明显相关。细胞角蛋白的预后价值显示出相互矛盾的结果，需要进一步研究以确定它们在预测口腔白斑病恶性转化中的作用。
