Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bommasandra Indl Area, Bangalore, India; Department of Head and Neck Surgery, Mazumdar Shaw Medical Center, Narayana Health, Bommasandra, Bengaluru, India; Department of Oral Maxillofacial and Plastic Surgery, University Medicine Rostock, Rostock, Germany; Proteome Center Rostock, University Medicine Rostock, Rostock, Germany.
Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bommasandra Indl Area, Bangalore, India.
Oral Oncol. 2018 Mar;78:207-215. doi: 10.1016/j.oraloncology.2018.01.017. Epub 2018 Feb 20.
The aim of this study was to determine whether intra-oral de novo regenerated mucosa (D) that grew over free fibula flap reconstructed-mandibles resembled the donor tissue i.e. external skin (S) of the lateral leg, or the recipient site tissue, i.e. keratinized oral mucosa (K).
Differential proteome analysis was performed with ten tissue samples from each of the three groups: de novo regenerated mucosa (D), external skin (S), and keratinized oral mucosa (K). Expression differences of cornulin and involucrin were validated by Western blot analysis and their spatial distributions in the respective tissues were ascertained by immunohistochemistry.
From all three investigated tissue types a total of 1188 proteins were identified, 930 of which were reproducibly and robustly quantified by proteome analysis. The best differentiating proteins were assembled in an oral mucosa proteome signature that encompasses 56 differentially expressed proteins. Principal component analysis of both, the 930 quantifiable proteins and the 56 oral mucosa signature proteins revealed that the de novo regenerated mucosa resembles keratinized oral mucosa much closer than extra-oral skin. Differentially expressed cornification-related proteins comprise proteins from all subclasses of the cornified cell envelope. Prominently expressed in intra-oral mucosa tissues were (i) cornifin-A, cornifin-B, SPRR3, and involucrin from the cornified-cell-envelope precursor group, (ii) S100A9, S100A8 and S100A2 from the S100 group, and (iii) cornulin which belongs to the fused-gene-protein group.
According to its proteome signature de novo regenerated mucosa over the free fibula flap not only presents a passive structural surface layer but has adopted active tissue function.
本研究旨在确定游离腓骨瓣重建下颌后新生成的口腔内黏膜（D）是否与供体组织（即小腿外侧的皮肤[S]）或受区组织（即角化口腔黏膜[K]）相似。
对每组 10 个组织样本进行差异蛋白质组分析，包括新生成的黏膜（D）、外部皮肤（S）和角化口腔黏膜（K）。通过 Western blot 分析验证了 Cornulin 和 Involucrin 的表达差异，并通过免疫组织化学确定了它们在各自组织中的空间分布。
从所有三种研究的组织类型中共鉴定出 1188 种蛋白质，其中 930 种通过蛋白质组分析可重复性和稳健性地定量。最佳区分蛋白被组装成一个口腔黏膜蛋白质组特征，包含 56 个差异表达蛋白。930 种可定量蛋白质和 56 种口腔黏膜特征蛋白的主成分分析表明，新生成的黏膜与角化口腔黏膜的相似性远大于口腔外皮肤。差异表达的角质化相关蛋白包含角质细胞包膜所有亚类的蛋白。在口腔内黏膜组织中高表达的有：（i）来源于角蛋白前体包膜组的角蛋白-10、角蛋白-14、丝聚合蛋白 3 和 Involucrin；（ii）来源于 S100 组的 S100A9、S100A8 和 S100A2；以及（iii）属于融合基因蛋白组的 Cornulin。
根据其蛋白质组特征，游离腓骨瓣重建后的新生成黏膜不仅提供了被动的结构表面层，而且还具有活跃的组织功能。
