Abstract:
It has been found that progression from leukoplakia to head and neck squamous cell carcinoma (HNSCC) is a long-term process that may involve changes in the multicellular ecosystem. We acquired scRNA-seq samples information from gene expression omnibus and UCSC Xena database. The BEAM function was used to construct the pseudotime trajectory and analyze the differentially expressed genes in different branches. We used the ssGSEA method to explore the correlation between each cell subgroup and survival time, and obtained the cell subgroup related to prognosis. During the progression from leukoplakia to HNSCC, we found several prognostic cell subgroups, such as AURKB + epithelial cells, SFRP1 + fibroblasts, SLC7A8 + macrophages, FCER1A + CD1C + dendritic cells, and TRGC2 + NK/T cells. All cell subgroups had two different fates, one tending to cell proliferation, migration, and enhancement of angiogenesis capacity, and the other tending to inflammatory immune response, leukocyte chemotaxis, and T cell activation. Tumor-promoting genes such as CD163 and CD209 were highly expressed in the myeloid cells, and depletion marker genes such as TIGIT, LAG3 were highly expressed in NK/T cells. Our study may provide a reference for the molecular mechanism of HNSCC and theoretical basis for the development of new therapeutic strategies.
摘要:
已经发现,从白斑到头颈部鳞状细胞癌(HNSCC)的进展是一个长期过程,可能涉及多细胞生态系统的变化。我们从基因表达综合和UCSCXena数据库获得了scRNA-seq样本信息。利用BEAM函数构建假时轨迹,分析不同分支的差异表达基因。我们使用ssGSEA方法来探索每个细胞亚群与生存时间之间的相关性,并获得与预后相关的细胞亚群。在从白斑发展到HNSCC的过程中,我们发现了几个预后细胞亚群,如AURKB+上皮细胞,SFRP1+成纤维细胞,SLC7A8+巨噬细胞,FCER1A+CD1C+树突状细胞,和TRGC2+NK/T细胞。所有细胞亚群都有两种不同的命运,一个倾向于细胞增殖,迁移,增强血管生成能力,另一种倾向于炎症免疫反应,白细胞趋化性,和T细胞激活。肿瘤促进基因如CD163和CD209在骨髓细胞中高表达,和耗竭标记基因,如TIGIT,LAG3在NK/T细胞中高表达。本研究可为探讨HNSCC的分子机制提供参考,为开发新的治疗策略提供理论依据。