在体细胞和单细胞水平上识别和分析口腔鳞状细胞癌的细胞通讯预后特征

Xingwei Zhang, Fan Yang, Chen Dong, Baojun Li, Shuo Zhang, Xiaohui Jiao, Dong Chen
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摘要

头颈部鳞状细胞癌(HNSC)是一种预后不良的异质性恶性肿瘤疾病,已成为当前全球关注的主要公共卫生问题。口腔鳞状细胞癌(OSCC)是头颈部鳞癌的主要类型。目前在临床实践中还缺乏全面的肿瘤免疫微环境分析和预后模型的建立。研究人员通过R软件包 "Seurat"、"Harmony"、"elldex "和 "CellChat "进行了单细胞测序数据分析,以确定OSCC中的免疫细胞亚型并说明细胞与细胞之间的相互作用状态。在大量测序数据的基础上,采用 WGCNA 分析来确定 CD8+ T 细胞相关基因模块。XGBoost 被用来构建 OSCC 的基因预后模型。对验证集和免疫治疗数据集进行了分析,以进一步评估该模型的有效性和免疫治疗反应性预测潜力。实时 PCR 和 Western 印迹用于验证靶基因的表达。通过伤口愈合、Trans井和克隆形成试验检测了FCRL4对OSCC细胞的影响。上皮细胞和组织干细胞之间的交流可能是OSCC进展的潜在关键调控因子。通过整合单细胞测序数据分析和大容量测序数据分析,我们构建了一个新的免疫相关基因预后模型。该模型能有效预测OSCC患者的预后和免疫治疗反应性。此外,我们还验证了 FCRL4 对 OSCC 细胞的影响。基于单细胞测序数据和大容量测序数据分析,我们全面解读了OSCC的免疫微环境模式。我们建立了一个基于免疫特征的稳健预后模型,用于精确评估OSCC的治疗和预后。
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Identification and analysis of a cell communication prognostic signature for oral squamous cell carcinoma at bulk and single-cell levels

Head and neck squamous cancer (HNSC) is a heterogenous malignant tumour disease with poor prognosis and has become the current major public health concern worldwide. Oral squamous cell carcinoma (OSCC) is the majority of HNSC. It is still in lack of comprehensive tumour immune microenvironment analysis and prognostic model development for OSCC's clinic practice. Single-cell sequencing data analysis was conducted to identify immune cell subtypes and illustrate cell–cell interaction status in OSCC via R package ‘Seurat’, ‘Harmony’, ‘elldex’ and ‘CellChat’. Base on the bulk sequencing data, WGCNA analysis was employed to identify the CD8+ T cell related gene module. XGBoost was used to construct the gene prognostic model for OSCC. Validation sets and immunotherapy data sets were analysed to further evaluate the model's effectiveness and immunotherapy responsiveness predicting potential. siRNA was used to down regulate FCRL4 expression. Real-time PCR and Western blot were used to validate target gene expression. The effects of FCRL4 on OSCC cells were detected by wound healing, Trans well and clone formation assays. Communication between epithelial cells and tissue stem cells may be the potential key regulators for OSCC progression. By integrating single-cell sequencing data analysis and bulk sequencing data analysis, we constructed a novel immune-related gene prognostic model. The model can effectively predict the prognosis and immunotherapy responsiveness of OSCC patients. In addition, the effects of FCRL4 on OSCC cells were validated. We comprehensively interpreted the immune microenvironment pattern of OSCC based on the single-cell sequencing data and bulk sequencing data analysis. A robust immune feature-based prognostic model was developed for the precise treatment and prognosis evaluation of OSCC.

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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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