[Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through
Xiaomeng Ren1, Kaiyi Li1, Chunlei Li1
1Department of Oral Medicine, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China.
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.
Insights
Gene expression profiles predict oral lichen planus response to dexamethasone. High expression of CLDN8, CTNNA3, MYL2, and MYLPF indicates good response, while inflammation pathway genes suggest poor outcomes.
Area of Science:
- Genomics and Molecular Biology
- Dermatology and Oral Medicine
- Pharmacogenomics
Context:
- Oral lichen planus (OLP) is a chronic inflammatory condition affecting oral mucosa.
- Topical glucocorticoids, like dexamethasone, are standard treatments for OLP.
- Predicting treatment response is crucial for optimizing patient care.
Purpose:
- To identify key genes associated with the therapeutic efficacy of topical dexamethasone in OLP patients using transcriptome sequencing.
- To correlate gene expression patterns with clinical outcomes of dexamethasone treatment.
Summary:
- Transcriptome sequencing was performed on 28 OLP patients before treatment with topical dexamethasone.
- Patients were categorized into effective and ineffective groups based on clinical response.
- Differentially expressed genes (DEGs) were identified, with upregulated genes (e.g., CLDN8, CTNNA3, MYL2, MYLPF) linked to leukocyte migration and downregulated genes associated with inflammatory pathways (TNF, IL-17, NF-κB) and cortisol synthesis.
Impact:
- Identifies specific genes (CLDN8, CTNNA3, MYL2, MYLPF) associated with positive dexamethasone response in OLP.
- Highlights the role of inflammatory pathways (TNF, IL-17, NF-κB) in predicting poor treatment outcomes.
- Provides a molecular basis for personalized treatment strategies in OLP management.
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