类风湿性关节炎患者滑膜组织lncRNA HCP5表达上调并与免疫细胞浸润相关  

The expression of long non⁃coding RNA human leukocyte antigen complex P5(lncRNA HCP5)in synovial tissue of patients with rheumatoid arthritis is up⁃regulated and correlated with immune cell infiltration

作　　者：肖剑伟 蔡旭 黄新民 郭粉莲 陈新鹏 洪易炜 尹志华 叶志中 XIAO Jianwei;CAI Xu;HUANG Xinmin;GUO Fenlian;CHEN Xinpeng;HONG Yiwei;YIN Zhihua;YE Zhizhong(Shenzhen Futian Hospital for Rheumatic Diseases,Shenzhen 518000,China)

机构地区：[1]深圳市福田区风湿病专科医院,广东深圳518000

出　　处：《细胞与分子免疫学杂志》2023年第5期445-450,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81102266);深圳市福田区卫生公益性科研项目(FTWS2020053)。

摘　　要：目的通过机器学习筛选类风湿性关节炎(RA)滑膜中潜在发病相关长链非编码RNA(lncRNA)及与各种免疫细胞浸润的相关性。方法通过基因表达数据集(GEO)数据库获取多个RA滑膜的基因芯片数据,归一化后通过多种机器学习方法筛选并取交集得到关键的lncRNA。使用估计已知RNA转录本的相对子集识别细胞类型(CIBER⁃SORT)算法计算滑膜中22种免疫细胞浸润情况,计算关键lncRNA与免疫细胞的相关性,最后通过实时定量PCR验证关键lncRNA在RA滑膜细胞中表达情况。结果筛选出RA关键lncRNA人类白细胞抗原复合物P5(lncRNA HCP5)。免疫浸润分析显示,在RA滑膜组织中,CD8+T细胞、γδT细胞、M1型巨噬细胞比例升高而M2型巨噬细胞的比例减少。lncRNA HCP5的表达与CD8+T细胞、γδT细胞、M1型巨噬细胞呈正相关。实时定量PCR结果显示在RA滑膜细胞lncRNA HCP5表达上调。结论lncRNA HCP5在RA滑膜细胞表达上调,可能与滑膜免疫细胞的浸润有关。Objective To identify the potential long non⁃coding RNA(lncRNA)expressed in rheumatoid arthritis(RA)synovium key to RA onset and investigate its association with immune cell infiltration.Methods RA synovium data were downloaded from the GEO database and normalized.The lncRNAs key to RA onset were identified using multiple machine learning methods.Infiltration of 22 immune cell populations in RA synovium was measured by cell⁃type identification by estimating relative subsets of RNA transcripts(CIBER⁃SORT).The relationship between the key lncRNA and infiltrating immune cells was analyzed.Finally,real⁃time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells.Results lncRNA human leukocyte antigen complex P5(HCP5)was identified as the key lncRNA associated with RA onset.Infiltration analysis revealed increased abundance of CD8+T cells,γδT cells,and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue.Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8+T cells,γδT cells,and M1 macrophages in RA synovial tissue.Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up⁃regulated.Conclusion lncRNA HCP5 expression is up⁃regulated in RA synovial tissue and potentially associated with immune cells infiltration.

关 键 词：类风湿性关节炎(RA) 机器学习 长链非编码RNA人类白细胞抗原复合物P5(lncRNA HCP5) 免疫浸润 

分 类 号：R255.6[医药卫生—中医内科学] Q811.4[医药卫生—中医学] R593.22[生物学—生物工程] R364.5