摘要
目的:探讨E2F转录因子5(E2F5)在口腔鳞状细胞癌(OSCC)中的表达模式,对细胞增殖的影响及其与免疫微环境的关系。方法:利用10X Genomics Visium平台空间转录组数据分析E2F5的空间分布特征;基于单细胞RNA测序数据,分析E2F5在不同细胞亚群中的表达模式;整合多中心数据,采用标准化均数差(SMD)和汇总受试者工作特征曲线(sROC)评估E2F5表达水平;并且分析E2F5表达与临床病理参数的关系;应用CRISPR敲除筛选技术评估E2F5对细胞增殖的影响;评估E2F5与免疫浸润的相关性。结果:空间转录组显示E2F5在OSCC肿瘤上皮区域呈高表达,与KRT5、KRT14、TP63等标志物空间共定位。单细胞测序分析679641个细胞发现,E2F5主要在上皮细胞亚群高表达,尤其在KRT5+/KRT14+/TP63+/MKI67+增殖性上皮细胞中表达突出。E2F5 mRNA在OSCC组织中显著上调(SMD=0.28,95%CI=0.06~0.51)。E2F5高表达与T分期、淋巴结转移、临床分期、病理分级、性别、种族及饮酒史等显著相关(P<0.05)。CRISPR敲除显示E2F5缺失显著抑制OSCC细胞增殖(SCORE<0)。免疫浸润分析显示E2F5高表达与多种免疫细胞富集呈负相关。结论:E2F5可能通过调控细胞周期及免疫微环境促进OSCC细胞增殖。
Objective To investigate the expression pattern of E2F Transcription Factor 5(E2F5)in oral squamous cell car⁃cinoma(OSCC),its effect on cell proliferation,and its relationship with the immune microenvironment.Methods Spatial transcriptomic data from the 10X Genomics Visium platform were used to analyze the spatial distribution of E2F5.Singlecell RNA sequencing data were used to analyze the expression patterns of E2F5 across different cell subpopulations.Multicenter data were integrated to assess the expressions of E2F5 using standardized mean difference(SMD)and summary re⁃ceiver operating characteristic(sROC)curves.The relationship between E2F5 and clinicopathological parameters was also analyzed.CRISPR knockout screening was applied in evaluating,the effect of E2F5 on cell proliferation,and the correla⁃tion between E2F5 and immune infiltration was evaluated.Results Spatial transcriptomics revealed that E2F5 was expressed at high levels in the tumor epithelial regions of OSCC,and spatially co-localized with markers including KRT5,KRT14,and TP63.Single-cell sequencing analysis of 679,641 cells indicated that E2F5 was predominantly highly expressed in epi⁃thelial cell subpopulations,particularly in KRT5+/KRT14+/TP63+/MKI67+proliferative epithelial cells.E2F5 mRNA was significantly upregulated in OSCC tissues(SMD=0.28,95%CI=0.06-0.51).High E2F5 expression had a remarkable association with T stage,lymph node metastasis,clinical stage,histological grade,gender,race,and the history of alcohol consumption(P<0.05).CRISPR knockout screening demonstrated that OSCC cell proliferation was markedly inhibited after E2F5 depletion(SCORE<0).It was found from immune infiltration analysis that high E2F5 expression was negatively cor⁃related with multiple immune cell enrichment scores.Conclusion E2F5 promotes the OSCC cell proliferation possibly by regulating the cell cycle and the immune microenvironment.
作者
吴科俊
张嘉铭
李玉锋
李建棣
莫弘博
王娜
陈国强
陈瑜
陈罡
李东明
WU Ke-jun;ZHANG Jia-ming;LI Yu-feng;LI Jian-di;MO Hong-bo;WANG Na;CHEN Guo-qiang;CHEN Yu;CHEN Gang;LI Dong-ming(Pathology Department of the First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530021,China;Pathology Department of Lingshan County People's Hospital,Lingshan,Guangxi 535400,China)
出处
《湖北医药学院学报》
2025年第6期663-671,共9页
Journal of Hubei University of Medicine
基金
广西壮族自治区卫生健康委员会科研项目(Z-A20220459)。
