阴茎硬化性苔藓相关尿道狭窄的组织病理和转录组特点

Histopathological and transcriptomic characteristics of male genital lichen sclerosus associated urethral stricture

目的通过组织病理学探究阴茎硬化性苔藓相关尿道狭窄组织的炎症特点,并通过转录组测序探究其分子改变及免疫细胞浸润特点。方法评估24例阴茎硬化性苔藓相关尿道狭窄(MGLS-US)患者与22例非阴茎硬化性苔藓相关的前尿道狭窄患者(AUS)的尿道狭窄临床特征及炎症特点。并对5例MGLS-US患者及5例AUS患者的尿道狭窄组织进行了转录组测序,进一步探究MGLS-US的生物学过程、信号通路及免疫细胞浸润改变。结果在炎症特点上,通过组织病理学检查显示MGLSc-US与重度炎症特点显著关联,而AUS与轻度炎症特点显著关联。MGLSc-US转录组测序分析表明,MGLS-US上调固有免疫、适应性免疫、T细胞激活、细胞杀伤等生物学过程及上调细胞因子与细胞因子作用、干扰素等相关免疫通路。免疫浸润分析显示,M1型巨噬细胞、CD8 T细胞及滤泡辅助性T细胞在MGLSc-US中占比更高。结论阴茎硬化性苔藓所致的尿道狭窄相较于非阴茎硬化性苔藓所致的尿道狭窄具有更为显著的慢性炎症特点,其中T淋巴细胞激活、细胞杀伤功能、干扰素通路、细胞因子相互作用为其转录组特征。

Objective To investigate the inflammatory characteristics of urethral strictures associated with penile lichen sclerosus(MGLS-US)through histopathology and explore molecular changes and immune cell infiltration using transcriptome sequencing.Methods Clinical characteristics and inflammatory features of urethral strictures in 24 patients with MGLS-US and 22 patients with non-male genital lichen sclerosus-related anterior urethral strictures(AUS)were assessed.Transcriptome sequencing was performed on urethral stricture tissues from 5 MGLS-US patients and 5 AUS patients to further explore the biological processes,signaling pathways,and immune cell infiltration changes in MGLS-US.Results Histopathological examination revealed a significant association between MGLS-US and severe inflammatory features,and between AUS and mild inflammatory features.Transcriptome sequencing analysis of MGLS-US indicated upregulation of biological processes such as innate immunity,adaptive immunity,T cell activation,and cell killing,as well as upregulation of immune pathways related to cytokines,cytokine action,interferon,and others.Immune cells filtration analysis showed a higher proportion of M1 macrophages,CD8 T cells,and follicular helper T cells in MGLS-US.Conclusion Urethral strictures caused by male genital lichen sclerosus exhibit more pronounced chronic inflammatory characteristics compared to those caused by non-male genital lichen sclerosus.Their transcriptome features include activation of T lymphocytes,cell killing functions,interferon pathways,and cytokine interactions.