头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析

doi:10.13418/j.issn.1001-165x.2024.2.10

中国临床解剖学杂志 ›› 2024, Vol. 42 ›› Issue (2): 174-180.doi: 10.13418/j.issn.1001-165x.2024.2.10

头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析

侯晓睿¹，李浩坤¹，宋贻芳¹，常若水¹，薛小磊²，张千兵³，吴砂^1，4，王妮莎⁵*

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

收稿日期:2023-11-14 出版日期:2024-03-25 发布日期:2024-04-22
作者简介:侯晓睿（1983-），女，硕士，实验师，主要从事抗感染免疫研究，E-mail:xiaoruihh@163.com
基金资助:
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）

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

Hou Xiaorui¹, Li Haokun¹, Song Yifang¹, Chang Ruoshui¹, Xue Xiaolei², Zhang Qianbing³, Wu Sha^1,4, Wang Nisha⁵*

1.Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangdong Provincial Key Laboratory of Functional Proteomics, Guangzhou 510515, China; 2.Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 3.Institute of Cancer, School of Basic Medicine, Southern Medical University, Guangzhou 510515, China; 4.National Medical Basic Experimental Teaching Demonstration Center, Guangzhou 510515, China; 5.Department of Biochemistry, School of Basic Medicine, Southern Medical University, Guangzhou 510515, China

Received:2023-11-14 Online:2024-03-25 Published:2024-04-22

摘要/Abstract

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。

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

Abstract: 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 SPP1 may be a valuable prognostic biomarker in HNSCC.

Key words: HNSCC, , , , SPP1, , , , Tumor-associated macrophages(TAM)

中图分类号:

R739.91

侯晓睿, 李浩坤, 宋贻芳, 常若水, 薛小磊, 张千兵, 吴砂, 王妮莎. 头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析[J]. 中国临床解剖学杂志, 2024, 42(2): 174-180.

Hou Xiaorui, Li Haokun, Song Yifang, Chang Ruoshui, Xue Xiaolei, Zhang Qianbing, Wu Sha, Wang Nisha. Screening and analysis of key genes in macrophages of head and neck squamous cell carcinoma [J]. Chinese Journal of Clinical Anatomy, 2024, 42(2): 174-180.

参考文献

[1] Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers,2020,6(1):92. DOI: 10.1038/s41572-020-00224-3.
[2] Mhaidly N, Journe F, Najem A, et al. Macrophage profiling in head and neck cancer to improve patient prognosis and assessment of cancer cell-macrophage interactions using three-dimensional coculture models[J]. Int J Mol Sci,2023,24(16). DOI: 10.3390/ijms241612813.
[3] Seminerio I, Kindt N, Descamps G, et al. High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus[J]. Oncotarget, 2018, 9(13):11046-11059. DOI:10.18632/oncotarget.24306.
[4] Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression[J]. Cancer Res, 2019,79(18):4557-4566. DOI:10.1158/0008-5472.CAN-18-3962.
[5] Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity[J]. Annu Rev Pathol, 2020, 15:123-147. DOI: 10.1146/annurev-pathmechdis-012418-012718.
[6] Qi J, Sun H, Zhang Y, et al. Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer[J]. Nat Commun, 2022,13(1):1742. DOI: 10.1038/s41467-022-29366-6.
[7] Ruffin AT, Cillo AR, Tabib T, et al. B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma[J]. Nat Commun, 2021,12(1):3349. DOI: 10.1038/s41467-021-23355-x.
[8] Cheng HY, Hsieh CH, Lin PH, et al. Snail-regulated exosomal microRNA-21 suppresses NLRP3 inflammasome activity to enhance cisplatin resistance[J]. J Immunother Cancer, 2022,10(8): e004832. DOI: 10.1136/jitc-2022-004832.
[9] Mody MD, Rocco JW, Yom SS, et al. Head and neck cancer[J]. Lancet, 2021, 398(10318):2289-2299. DOI: 10.1016/S0140-6736(21)01550-6.
[10] Peters S, Paz-Ares L, Herbst RS, et al. Addressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects[J]. J Immunother Cancer, 2022,10(7). DOI: 10.1136/jitc-2022-004863.
[11]Pittet MJ, Michielin O, Migliorini D. Clinical relevance of tumour-associated macrophages[J]. Nat Rev Clin Oncol,2022,19(6):402-421. DOI: 10.1038/s41571-022-00620-6.
[12] Christofides A, Strauss L, Yeo A, et al. The complex role of tumor-infiltrating macrophages[J]. Nat Immunol,2022, 23(8):1148-1156. DOI:10.1038/s41590-022-01267-2.
[13] Lamort AS, Giopanou I, Psallidas I, et al. Osteopontin as a link between inflammation and cancer: the thorax in the spotlight[J]. Cells,2019,8(8):815. DOI: 10.3390/cells8080815.
[14]Zhu Y, Yang J, Xu D, et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade[J]. Gut,2019,68(9):1653-1666. DOI: 10.1136/gutjnl-2019-318419.
[15]Bill R, Wirapati P, Messemaker M, et al. CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers[J]. Science, 2023, 381(6657):515-524. DOI:10.1126/science.ade2292.

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

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	刘子豪, 刘家明, 颜金祥, 吴嘉宝, 黄山虎, 张志宏, 刘志礼. 下颈椎新型双螺纹椎弓根螺钉设计的解剖学测量[J]. 中国临床解剖学杂志, 2024, 42(2): 121-125.
[2]	陈钧麟, 马向阳, 邹小宝, 付索超, 朱昌荣, 邓琛府, 马仁财, 陈泽星, 夏虹. C_2/3经关节突经椎弓根螺钉固定的影像学测量及可行性分析[J]. 中国临床解剖学杂志, 2024, 42(2): 126-130.
[3]	郑益钒, 陈嘉楠, 裴璇, 周唯, 方志勋, 程翼鹏, 刘曦明. 髋臼后柱壁安全置钉的数字化解剖研究[J]. 中国临床解剖学杂志, 2024, 42(2): 131-135.
[4]	杨涛, 高转, 刘炳智, 李武超, 孙睿哲, 郎昱颖, 李京. 尺侧副韧带后束的解剖学特征及临床意义[J]. 中国临床解剖学杂志, 2024, 42(2): 136-139.
[5]	卓航, 周泽霖, 邬裕, 龚焱, 宋泽峰, 颜先伟, 沈姿, 卢国樑, 梁德, 江晓兵, 余翔. 基于中老年MRI腰椎椎基静脉孔的影像解剖学研究[J]. 中国临床解剖学杂志, 2024, 42(2): 140-144.
[6]	李佳伟, 张凯, 丁良甲, 王海燕, 陈清威, 刘启, 于小明, 兰文杰, 李筱贺. 内蒙古地区样本髋关节置换假体位置数字化评估[J]. 中国临床解剖学杂志, 2024, 42(2): 145-152.
[7]	方源, 康志杰, 王海燕, 沙丽荣, 李筱贺, 金凤, 齐昕, 王彦超, 张云凤. 未成年人骶骨形态与耻骨联合相对位置三维数字化测量及临床意义[J]. 中国临床解剖学杂志, 2024, 42(2): 153-158.
[8]	吴嘉宝, 孙伯林, 邢锴, 张宁, 周荣平, 陈江伟, 刘志礼, 刘家明. 退行性腰椎侧凸椎管形态学特征及其与脊柱-骨盆参数的相关性分析[J]. 中国临床解剖学杂志, 2024, 42(2): 159-167.
[9]	杨先文, 王飞, 成赋斌, 廖立青. 封闭治疗肩周炎的应用解剖学研究[J]. 中国临床解剖学杂志, 2024, 42(2): 168-173.
[10]	孙丽, 李欣欣, 李跃, 葛明晓, 欧建平, 葛淑琦. 拮抗剂方案新鲜胚胎移植和冻融胚胎移植临床结局比较[J]. 中国临床解剖学杂志, 2024, 42(2): 181-185.
[11]	张凡, 韦焕杰, 李龙, 欧阳涛, 蔡娟, 梁秋玲, 曾育辉. 连翘苷对感染性休克小鼠急性肺损伤的作用与机制[J]. 中国临床解剖学杂志, 2024, 42(2): 186-190.
[12]	阮磊, 黄博, 王兰兰, 薛惠天, 孙梦龙, 段苗苗, 彭亮. 推拿扌衮法对骨骼肌钝挫伤家兔模型损伤后炎症及纤维化的影响[J]. 中国临床解剖学杂志, 2024, 42(2): 191-195.
[13]	刘瑞平, 钱蕾, 刘燕燕, 万心竹, 陈春艳, 王镱凝, 于宛琪, 欧阳钧. 有跌倒史老年人坐立运动过程中的肌肉协同分析[J]. 中国临床解剖学杂志, 2024, 42(2): 196-200.
[14]	张云浩, 范凯, 黄从军, 程强强, 王官燕, 肖友平, 梅傲冰. 基于CT数据融合的三维可视化技术及数字虚拟诊疗在肾上腺肿瘤的应用研究[J]. 中国临床解剖学杂志, 2024, 42(2): 201-207.
[15]	沈江江, 刘志红, 刘宝辉. 神经内镜联合显微镜微血管减压术治疗原发性三叉神经痛的疗效观察#br#[J]. 中国临床解剖学杂志, 2024, 42(2): 208-212.