School of Dental Medicine, Department of Oral Medicine, University of Zagreb, Zagreb, Croatia.
Department of Biotechnology and Centre for High-throughput technologies, University of Rijeka, Radmile Matejčić 2, 51000, Rijeka, Croatia.
Clin Oral Investig. 2018 Mar;22(2):1071-1082. doi: 10.1007/s00784-017-2190-3. Epub 2017 Aug 4.
The aim of this study was to examine molecular alterations on the protein level in lesions of oral lichen planus (OLP), oral squamous cell carcinoma (OSCC) and healthy mucosa.
Global protein profiling methods based on liquid chromatography coupled to mass spectrometry (LC-MS) were used, with a special emphasis on evaluation of deregulated extracellular matrix molecules expression, as well as on analyses of IG2F and IGFR2 expression in healthy mucosa, OLP and OSCC tissues by comparative semi-quantitative immunohistochemistry.
Mass spectrometry-based proteomics profiling of healthy mucosa, OLP and OSCC tissues (and accompanied histologically unaltered tissues, respectively) identified 55 extracellular matrix proteins. Twenty among identified proteins were common to all groups of samples. Expression of small leucine-rich extracellular matrix proteoglycans lumican and biglycan was found both in OSCC and OLP and they were validated by Western blot analysis as putative biomarkers. A significant increase (p < 0.05) of biglycan expression in OLP-AT group was determined in comparison with OLP-T group, while lumican showed significant up-regulation (p < 0.05) in OLP-T and OSCC-T groups vs. adjacent and control tissue groups. Biglycan expression was only determined in OSCC-AT group. Immunohistochemical analysis of IGF2 and IG2FR expression revealed no significant difference among groups of samples.
CONCLUSION/CLINICAL RELEVANCE: Biglycan and lumican were identified as important pathogenesis biomarkers of OLP that point to its malignant potential.
本研究旨在检测口腔扁平苔藓(OLP)、口腔鳞状细胞癌(OSCC)和正常黏膜病变组织中蛋白质水平的分子改变。
采用基于液相色谱-质谱联用(LC-MS)的全局蛋白质谱分析方法,特别关注细胞外基质分子表达失调的评估,以及通过比较半定量免疫组织化学分析正常黏膜、OLP 和 OSCC 组织中 IG2F 和 IGFR2 的表达。
对正常黏膜、OLP 和 OSCC 组织(分别对应相应的组织学无改变组织)进行基于质谱的蛋白质组学分析,共鉴定出 55 种细胞外基质蛋白。其中 20 种蛋白在所有样本组中均有表达。在 OSCC 和 OLP 中均发现了小富含亮氨酸的细胞外基质蛋白聚糖(lumican)和 biglycan 的表达,Western blot 分析验证了它们是潜在的生物标志物。与 OLP-T 组相比,OLP-AT 组 biglycan 的表达显著增加(p<0.05),而 OLP-T 和 OSCC-T 组与相邻和对照组织组相比,lumican 的表达显著上调(p<0.05)。仅在 OSCC-AT 组中检测到 biglycan 的表达。IGF2 和 IG2FR 的免疫组化分析显示各组样本之间无显著差异。
结论/临床相关性:biglycan 和 lumican 被鉴定为 OLP 的重要发病机制生物标志物,表明其具有恶性潜能。