头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析  

Screening and analysis of key genes in macrophages of head and neck squamous cell carcinoma

作　　者：侯晓睿 李浩坤 宋贻芳 常若水 薛小磊[2] 张千兵[3] 吴砂 王妮莎[5] Hou Xiaorui;Li Haokun;Song Yifang;Chang Ruoshui;Xue Xiaolei;Zhang Qianbing;Wu Sha;Wang Nisha(Department of Immunology,School of Basic Medical Sciences,Southern Medical University,Guangdong Provincial Key Laboratory of Functional Proteomics,Guangzhou 510515,China;Department of Pathology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Institute of Cancer,School of Basic Medicine,Southern Medical University,Guangzhou 510515,China;National Medical Basic Experimental Teaching Demonstration Center,Guangzhou 510515,China;Department of Biochemistry,School of Basic Medicine,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学基础医学院免疫学教研室,广东省功能蛋白质组学重点实验室,广州510515 [2]南方医科大学南方医院病理科,广州510515 [3]南方医科大学基础医学院肿瘤研究所,广州510515 [4]国家医学基础实验教学示范中心,广州510515 [5]南方医科大学基础医学院生物化学教研室,广州510515

出　　处：《中国临床解剖学杂志》2024年第2期174-180,共7页Chinese Journal of Clinical Anatomy

基　　金：国家自然科学基金面上项目(No.82073165);广东省医学科学技术研究基金项目(No.A2023124)。

摘　　要：目的 应用生物信息学的方法分析筛选头颈部鳞状细胞癌(HNSCC)巨噬细胞中的潜在关键基因,为HNSCC的预后提供靶点。方法 基于在线数据库,利用一致流形近似与投影(UMAP)降维,捕获巨噬细胞群;进一步通过t-分布随机近邻嵌入(tSNE)聚类降维分析肿瘤组织与正常组织细胞群分布的变化并筛选差异基因的表达;运用Monocle包对关键风险基因在不同发育阶段细胞中的表达情况进行分析;利用Kaplan-Meier Plotter在线数据平台分析生存曲线;运用空间转录组技术验证关键基因在组织中的表达映射;多色荧光免疫组化进行临床样本的验证。结果 捕获得到7个巨噬细胞亚群,其中第1亚群仅存在于肿瘤组织中且分泌型磷蛋白1(SPP1)基因高富集。SPP1高表达趋向巨噬细胞M2型极化并处于细胞分化的终末阶段。SPP1+巨噬细胞糖酵解、缺氧、上皮间质化、血管生成等功能活跃,与HNSCC患者的预后呈负相关。结论 SPP1可能成为HNSCC中有价值的预后生物标志物。Objective To analyze and screen potential key genes in macrophages of head and neck squamous cell carcinoma(HNSCC) by bioinformatics,and to provide a target for the prognosis of HNSCC.Methods The macrophage population was captured by using uniform manifold approximation and projection(UMAP) dimensionality reduction based on online database.Furthermore,T-distributed random neighbor embedding(tSNE) clustering was used to analyze the changes of cell population distribution in tumor tissue and normal tissue,and to screen the expression of differential genes.Monocle package was used to analyze the expression of key risk genes in cells at different developmental stages.The survival curve was analyzed using Kaplan-Meier Plotter online data platform.Spatial transcriptome technology was used to verify the expression mapping of key genes in tissues.Clinical samples were validated by multicolor fluorescence immunohistochemistry.Results Seven macrophage subgroups were captured,of which the first subgroup existed only in tumor tissue and SPP1 gene was highly enriched.The high expression of SPP1 tended to the M2-type polarization of macrophages and was in the terminal stage of cell differentiation.SPP1+macrophages had active functions such as glycolysis,hypoxia,epithelialization,and angiogenesis.The expression of SPP1+macrophages was negatively correlated with the prognosis of HNSCC patients.Conclusions SPP1may be a valuable prognostic biomarker in HNSCC.

关 键 词：头颈部鳞状细胞癌 分泌型磷蛋白1(SPP1) 肿瘤相关巨噬细胞 

分 类 号：R739.91[医药卫生—肿瘤]