Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.
Sci Rep. 2020 Dec 4;10(1):21292. doi: 10.1038/s41598-020-78339-6.
Recent advances in the field of biomedical research allow for elucidation of the transcriptional signature of rare tumors such as conjunctival squamous cell carcinoma (SCC). In this study we compare its expression profile to conjunctival papilloma (Pap) and healthy conjunctival tissue (Ctrl) and develop a classification tool to differentiate these entities. Seven conjunctival SCC, seven Pap and ten Ctrl were formalin-fixed and paraffin-embedded (FFPE) and analyzed using Massive Analysis of cDNA Ends (MACE) RNA sequencing. Differentially expressed genes (DEG) and gene ontology (GO) clusters were explored and the abundance of involved cell types was quantified by xCell. Finally, a classification model was developed to distinguish SCC from Pap and Ctrl. Among the most prominent DEG in SCC a plethora of keratins were upregulated when compared to Pap and Ctrl. xCell analysis revealed an enrichment of immune cells, including activated dendritic cells and T-helper type 1 cells (Th1), in SCC when compared to Ctrl. The generated classification model could reliably discriminate between the three entities according to the expression pattern of 30 factors. This study provides a transcriptome-wide gene expression profile of rare conjunctival SCC. The analysis identifies distinct keratins, as well as dendritic and Th1 cells as important mediators in SCC. Finally, the provided gene expression classifier may become an aid to the conventional histological classification of conjunctival tumors in uncertain cases.
生物医学研究领域的最新进展使得阐明罕见肿瘤（如结膜鳞状细胞癌[SCC]）的转录特征成为可能。在这项研究中，我们将其表达谱与结膜乳头瘤（Pap）和健康结膜组织（Ctrl）进行了比较，并开发了一种分类工具来区分这些实体。将 7 例结膜 SCC、7 例 Pap 和 10 例 Ctrl 进行福尔马林固定和石蜡包埋（FFPE），并使用大规模 cDNA 末端分析（MACE）RNA 测序进行分析。探索差异表达基因（DEG）和基因本体（GO）聚类，并通过 xCell 定量分析涉及的细胞类型的丰度。最后，开发了一种分类模型来区分 SCC、Pap 和 Ctrl。与 Pap 和 Ctrl 相比，SCC 中大量角蛋白上调。xCell 分析表明，与 Ctrl 相比，SCC 中免疫细胞，包括活化的树突状细胞和 T 辅助细胞 1（Th1），富集。根据 30 个因素的表达模式，生成的分类模型可以可靠地区分这三种实体。这项研究提供了罕见结膜 SCC 的全转录组基因表达谱。分析确定了独特的角蛋白，以及树突状细胞和 Th1 细胞作为 SCC 的重要介质。最后，提供的基因表达分类器可能成为不确定病例中结膜肿瘤常规组织学分类的辅助手段。
