摘要目的:探讨肿瘤坏死因子受体超家族成员10B(TNFRSF10B)在瘢痕疙瘩(Keloid)与正常瘢痕组织中的表达差异及其潜在生物学功能。方法:本研究利用单细胞RNA测序数据(2021年5月23日公开)进行分析，经严格质量控制后，最终纳入40 655个细胞的转录组数据，包括瘢痕疙瘩组织样本( n＝3)的21 488个细胞和正常疤痕组织样本( n＝3)的19 167个细胞。研究重点考察了TNFRSF10B在瘢痕疙瘩与正常瘢痕组织中的表达差异，特别关注其在成纤维细胞亚群中的分布特征。整合了多个RNA-seq数据集以比较两种组织中TNFRSF10B的差异表达，并通过广西医科大学第一附属医院美容科临床样本验证。验证队列包括25例受试者(女17例，男8例，年龄18～43岁)，于2021年7月至11月期间采集的13例正常瘢痕组织和12例瘢痕疙瘩组织样本。进行了TNFRSF10B共表达基因分析与功能富集研究，并通过分子对接技术筛选了潜在靶向TNFRSF10B的小分子药物候选物。运用 P<0.05作为统计学显著性标准，根据异质性程度选择固定或随机效应模型计算标准化均数差，通过受试者工作特征曲线与汇总受试者工作特征曲线评估TNFRSF10B表达水平，并使用Begg’s检验排除发表偏倚。 结果:单细胞RNA测序结果显示，TNFRSF10B在瘢痕疙瘩的COL1A1/2 ＋、FAP ＋、PDGFRA ＋成纤维细胞亚型中的表达显著升高。高通量RNA-seq分析进一步证实，TNFRSF10B在瘢痕疙瘩中的表达水平高于正常瘢痕组织[SMD＝0.36，95%可信区间( CI)：0.03～0.70，AUC＝0.86]，并且在本院病例测序验证中得到进一步支持，TNFRSF10B在瘢痕疙瘩组织中高表达[瘢痕疙瘩比正常瘢痕组织，0.93比0.91， t＝3.207， P<0.05，曲线下面积(AUC)＝0.81]。共表达分析显示，TNFRSF10B与193个基因呈显著相关，这些基因主要富集在糖胺聚糖生物合成(尤其是硫酸软骨素/硫酸皮肤素的合成)和焦点黏附等通路中。分子对接分析结果提示，维莫德吉布等可能作为潜在的TNFRSF10B靶向药物。 结论:TNFRSF10B在瘢痕疙瘩组织中高表达，可能经糖胺聚糖生物合成途径(尤以硫酸软骨素/硫酸皮肤素合成突出)促使成纤维细胞过度增生，在瘢痕疙瘩病变中起重要作用。

abstractsObjective:To explore the differential expression of tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) in keloid tissue compared to normal scar tissue and its potential biological function, aiming to provide insights into the pathogenesis of keloids and potential therapeutic strategies.Methods:This study analyzed single-cell RNA sequencing data (published on May 23, 2021) and, after rigorous quality control, included transcriptome data from 40 655 cells, comprising 21 488 cells from keloid tissue samples ( n=3) and 19, 167 cells from normal scar tissue samples ( n=3). The research focused on examining the differential expression of TNFRSF10B in keloid versus normal scar tissues, with special attention to its distribution patterns in fibroblast subpopulations. Additionally, we integrated multiple RNA-seq datasets to compare TNFRSF10B expression differences between the two tissue types, with validation through clinical samples from the Department of Aesthetic Medicine, First Affiliated Hospital of Guangxi Medical University. The validation cohort included 25 subjects (17 females and 8 males, aged 18-43 years), with samples collected between July and November 2021, consisting of 13 normal scar tissue and 12 keloid tissue samples. The study also conducted TNFRSF10B co-expression gene analysis with functional enrichment studies, and screened potential small molecule drug candidates targeting TNFRSF10B through molecular docking techniques. A P-value < 0.05 was considered statistically significant. Fixed or random effects models were selected to calculate the standardized mean difference based on heterogeneity levels. Receiver operating characteristic curves and summary receiver operating characteristic curves were used to evaluate TNFRSF10B expression levels (with larger area under the curve indicating higher expression), and Begg’s test was employed to exclude publication bias. Results:Single-cell RNA sequencing revealed significantly elevated expression of TNFRSF10B in COL1A1/2 +, FAP +, and PDGFRA + fibroblast subtypes in keloid tissue. High-throughput RNA-seq further confirmed that TNFRSF10B expression was significantly higher in keloid tissue than in normal scar tissue [SMD=0.36, 95% confidence interval ( CI): 0.03-0.70, area under curve (AUC)=0.86], and this finding was further supported by clinical sample validation (Keloid vs. Normal scar tissue, Statistics=0.93 vs. 0.91, t=3.207, P<0.05, AUC=0.81). Co-expression analysis showed that TNFRSF10B was significantly correlated with 193 genes, which were mainly involved in glycosaminoglycan biosynthesis (especially the synthesis of chondroitin sulfate/dermatan sulfate) and focal adhesion pathways. Molecular docking analysis suggested that vildagliptin and chlorpheniramine might be potential small-molecule drugs targeting TNFRSF10B. Conclusion:TNFRSF10B is highly expressed in keloid tissues. It may promote the excessive proliferation of fibroblasts through the glycosaminoglycan biosynthesis pathway, especially highlighting the synthesis of chondroitin sulfate/dermatan sulfate, and plays an important role in the pathological process of keloids.