Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland; Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Transplantation Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014, Finland; HUSLAB, Helsinki University Hospital, Helsinki 00290, Finland.
Oral Oncol. 2018 Nov;86:206-215. doi: 10.1016/j.oraloncology.2018.09.013. Epub 2018 Oct 3.
No prognostic or predictive biomarkers for oral squamous cell carcinoma (OSCC) exist. We aimed to discover novel proteins, altered in OSCC, to be further investigated as potential biomarkers, and to improve understanding about pathways involved in OSCC.
Proteomic signatures of seven paired healthy and OSCC tissue samples were identified using ultra-definition quantitative mass spectrometry, then analysed and compared using Anova, principal component analysis, hierarchical clustering and OPLS-DA modelling. A selection of significant proteins that were also altered in the serum from a previous study (PMID: 28632724) were validated immunohistochemically on an independent cohort (n = 66) to confirm immunopositivity and location within tumour tissue. Ingenuity Pathways Analysis was employed to identify altered pathways.
Of 829 proteins quantified, 257 were significant and 72 were able to classify healthy vs OSCC using OPLS-DA modelling. We identified 19 proteins not previously known to be upregulated in OSCC, including prosaposin and alpha-taxilin. KIAA1217 and NDRG1 were upregulated in stage IVa compared with stage I tumours. Altered pathways included calcium signalling, cellular movement, haematological system development and function, and immune cell trafficking, and involved NF-kB and MAPK networks.
We found a set of proteins reliably separating OSCC tumour from healthy tissue, and multiple proteins differing between stage I and stage IVa OSCC. These potential biomarkers can be studied and validated in larger cohorts.
目前尚无口腔鳞状细胞癌（OSCC）的预后或预测生物标志物。本研究旨在发现 OSCC 中改变的新型蛋白质，进一步将其作为潜在的生物标志物进行研究，并深入了解 OSCC 相关通路。
使用超分辨率定量质谱技术鉴定了 7 对配对的健康和 OSCC 组织样本的蛋白质组学特征，然后使用 ANOVA、主成分分析、层次聚类和 OPLS-DA 模型进行分析和比较。在之前的研究（PMID: 28632724）中改变的血清中选择一些具有显著差异的蛋白质，然后在独立队列（n=66）中通过免疫组织化学进行验证，以确认肿瘤组织内的免疫阳性和位置。采用 Ingenuity 通路分析来识别改变的通路。
在所定量的 829 种蛋白质中，有 257 种是显著的，72 种可以使用 OPLS-DA 模型对健康与 OSCC 进行分类。我们鉴定了 19 种以前未知在 OSCC 中上调的蛋白质，包括 prosaposin 和 alpha-taxilin。与 I 期肿瘤相比，IVa 期肿瘤中 KIAA1217 和 NDRG1 上调。改变的通路包括钙信号转导、细胞运动、血液系统发育和功能以及免疫细胞迁移，涉及 NF-kB 和 MAPK 网络。
我们发现了一组可靠地区分 OSCC 肿瘤与健康组织的蛋白质，以及在 I 期和 IVa 期 OSCC 之间存在差异的多种蛋白质。这些潜在的生物标志物可以在更大的队列中进行研究和验证。
