目的: 探索影响口腔扁平苔藓(oral lichen planus, OLP)局部糖皮质激素治疗敏感性相关分子。方法: 本研究为前瞻性研究，纳入2019年11月至2023年3月就诊于北京大学口腔医院口腔黏膜科28例有症状的OLP患者，采用0.1 g/L(mg/mL)地塞米松局部涂擦，每日3次，每次1 min，治疗4周后根据其临床效果(体征记分、疼痛症状记分、口腔健康程度量表)将OLP分为激素有效组和激素无效组。治疗前收集受试者口腔黏膜组织，提取组织总核糖核酸(ribonucleic acid, RNA)后进行转录组测序。对测序获得的基因表达数据，使用R软件中的DESeq2包进行差异分析，基于超几何分布算法对差异表达基因(differentially expressed genes, DEGs)进行京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析，从而筛选可能影响局部地塞米松治疗敏感性的相关分子。结果: 28例OLP患者经过局部地塞米松治疗4周后，13例患者在治疗前后客观体征记分分别为7.0(4.5，9.0)和5.0(3.0，6.3)，疼痛症状记分分别为5.0(2.0，5.5)和2.0(0.0，3.5)，口腔健康影响程度分别为5.0(3.5，9.0)和1.0(0.0，5.0)，均显著降低(P＜0.01)(有效组)，15例患者治疗后上述指标与治疗前差异无统计学意义(无效组)，两组患者的一般情况及治疗前疾病严重程度差异无统计学意义(P>0.05)。两组患者转录组学测序共鉴定出499个DEGs，其中有效组中274个基因上调，225个基因下调。KEGG富集分析显示有效组上调基因显著富集于白细胞穿血管内皮迁移通路(CLDN8、CTNNA3、MYL2、MYLPF)，而下调基因显著富集于肿瘤坏死因子(tumor necrosis factor, TNF)、白介素-17(interleukin-17, IL-17)、核因子κB(nuclear factor kappa B, NF-κB)及皮质醇合成和分泌信号通路。结论: CLDN8、CTNNA3、MYL2、MYLPF高表达的OLP患者对局部糖皮质激素治疗效果较好，而对TNF、IL-17、NF-κB等炎症通路相关基因及皮质醇合成分泌相关基因高表达的患者治疗效果较差。

Objective: To detect key genes of local glucocorticoid therapy in oral lichen planus (OLP) through transcriptome sequencing. Methods: The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa, Peking University Hospital of Stomatology from November 2019 to March 2023. Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min, 3 times daily for 4 weeks. The patients' signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome. Their mucosa samples were collected before treatment. After isolating total RNA, transcriptome sequencing was performed. The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software, and the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes (DEGs), accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone. Results: After 4 weeks treatment by topical dexamethasone, 13 cases of the 28 OLP patients responding well with the sign score reducing from 7.0 (4.5, 9.0) to 5.0 (3.0, 6.3), pain score decreasing from 5.0 (2.0, 5.5) to 2.0 (0.0, 3.5), oral health impact profile lessening from 5.0 (3.5, 9.0) to 1.0 (0.0, 5.0) significantly (P<0.01) were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group. There were no significant differences of demographic and baseline levels of clinical features, especially disease severity between these two groups. A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between effective group and ineffective group. KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8, CTNNA3, MYL2 and MYLPF were associated with leukocyte transendothelial migration, while downregulated genes were significantly enriched in tumor necrosis factor (TNF), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB) signaling pathways, and cortisol synthesis and secretory. Conclusion: High expressions of CLDN8, CTNNA3, MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone, while patients with high expression genes of inflammation pathway such as TNF, IL-17, NF-κB and cortisol synthesis and secretion received poor effect.