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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (1): 32-38. doi: 10.19723/j.issn.1671-167X.2024.01.006

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Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing

Xiaomeng REN,Kaiyi LI,Chunlei LI*()   

  1. Department 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
  • Received:2023-10-11 Online:2024-02-18 Published:2024-02-06
  • Contact: Chunlei LI E-mail:lichunlei12@hotmail.com
  • Supported by:
    Grants from Young People Fund of Peking University School and Hospital of Stomatology(PKUSS20220103)

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Abstract:

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.

Key words: Oral lichen planus, Transcriptome analysis, Topical glucocorticoid treatment, Prospective study, Sensitivity related molecular

CLC Number: 

  • R781.5

Figure 1

Lesion conditions before and after treatment of two groups A and B, effective, erosion and reticulation lesion on lower lip disappeared after 4 weeks treatment; C and D, ineffective, reticulation lesion on ventral tongue was not improved after 4 weeks topical therapy. A and C, week 0; B and D, week 4."

Table 1

Demographics and baseline level of clinical features of OLP patients"

Items Effective group(n=13) Ineffective group(n=15) P value
Gender, n(%) 0.700
  Male 7 (41.2) 10 (58.8)
  Female 6 (54.5) 5 (45.5)
Age/years, ${\bar x}$±s 38.9±10.8 46.1±12.1 0.114
Smoking, n(%) 0.114
  Yes 2 (22.2) 7 (77.8)
  No 11 (57.9) 8 (42.1)
Drinking, n(%) 0.705
  Yes 4 (40.0) 6 (60.0)
  No 9 (50.0) 9 (50.0)
Spicy diet, n(%) 0.396
  Yes 11 (52.4) 10 (47.6)
  No 2 (28.6) 5 (71.4)
Family history of OLP, n(%) >0.999
  Yes 0 (0.0) 1 (100.0)
  No 13 (48.1) 14 (51.9)
Chief complaint, n(%) >0.999
  No discomfort 1 (50.0) 1 (50.0)
  Roughness 3 (50.0) 3 (50.0)
  Smarting sensation 9 (45.0) 11 (55.0)
Duration/months, M(P25, P75) 3 (1, 5) 3 (2, 6) 0.428
Clinical type, n(%) >0.999
  Erosive 2 (50.0) 2 (50.0)
  Nonerosive 11 (45.8) 13 (54.2)
RHU score, M(P25, P75) 7.0
(4.5，9.0)		 6.0
(3.0，7.0)		 0.110
VAS pain score, M(P25, P75) 5.0
(2.0，5.5)		 3.0
(3.0，5.0)		 0.594
OHIP score, M(P25, P75) 5.0
(3.5，9.0)		 5.0
(2.0，9.0)		 >0.999

Figure 2

Change of RHU, VAS, OHIP-14 score before and after treatment in effective and ineffective group # P<0.01. RHU, reticulation, hyperemia and ulceration; VAS, visual analogue scale; OHIP, oral health impact profile; BT, before treatment; AT, after treatment."

Figure 3

Volcano map of differentially expressed genes between effective group and ineffective group"

Figure 4

KEGG enrichment diagram of differentially expressed genes between effective group compared and ineffective group A, top 25 Kyoto encyclopedia of genes and genomes (KEGG) pathways enriched up-regulated differentially expressed genes (DEGs); B, top 25 KEGG pathways enriched down-regulated DEGs in effective group compared to ineffective group according to the P value. PPAR, peroxisome proliferators-activated receptors; TNF, tumor necrosis factor; NF-kappa B, nuclear factor kappa B; IL-17, interleukin-17."

Figure 5

Transcript expression associated with effect of topical glucocorticoid of OLP FPKM, fragments per kilobase of exon model per million mapped fragments. EG, effective group; IEG, ineffective group; OLP, oral lichen planus."

1 Li C , Tang X , Zheng X , et al. Global prevalence and incidence estimates of oral lichen planus: A systematic review and meta-analysis[J]. JAMA Dermatol, 2020, 156 (2): 172- 181.
doi: 10.1001/jamadermatol.2019.3797
2 Li JW , Li KY , Chan BWA , et al. Rate of malignant transformation differs based on diagnostic criteria for oral lichenoid conditions: A systematic review and meta-analysis of 24 277 patients[J]. Cancers (Basel), 2023, 15 (9): 2537.
doi: 10.3390/cancers15092537
3 Zhu ZD , Ren XM , Zhou MM , et al. Salivary cytokine profile in patients with oral lichen planus[J]. J Dent Sci, 2022, 17 (1): 100- 105.
doi: 10.1016/j.jds.2021.06.013
4 Ioannides D , Vakirlis E , Kemeny L , et al. European S1 guidelines on the management of lichen planus: A cooperation of the european dermatology forum with the european academy of dermatology and venereology[J]. J Eur Acad Dermatol Venereol, 2020, 34 (7): 1403- 1414.
doi: 10.1111/jdv.16464
5 中华口腔医学会口腔黏膜病学专业委员会, 中华口腔医学会中西医结合专业委员会. 口腔扁平苔藓诊疗指南(修订版)[J]. 中华口腔医学杂志, 2022, 57 (2): 115- 121.
doi: 10.3760/cma.j.cn112144-20211115-00505
6 左雯鑫, 李晓宇, 蔡淦英, 等. 他克莫司含漱液治疗糜烂型口腔扁平苔藓的随机单盲对照研究[J]. 上海口腔医学, 2013, 22 (6): 708- 710.
7 Jajarm HH , Falaki F , Mahdavi O . A comparative pilot study of low intensity laser versus topical corticosteroids in the treatment of erosive-atrophic oral lichen planus[J]. Photomed Laser Surg, 2011, 29 (6): 421- 425.
doi: 10.1089/pho.2010.2876
8 Qing M , Zhou Y , Peng J , et al. The interleukin-6 family in tissues is closely related to the clinical outcomes of oral lichen planus[J]. J Oral Pathol Med, 2023, 52 (2): 161- 168.
doi: 10.1111/jop.13366
9 van der Meij EH , van der Waal I . Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications[J]. J Oral Pathol Med, 2003, 32 (9): 507- 512.
doi: 10.1034/j.1600-0714.2003.00125.x
10 Wu Y , Xu H , Wang Y , et al. An improved scoring system for monitoring oral lichen planus: A preliminary clinical study[J]. Oral Dis, 2023, 29 (8): 3337- 3345.
doi: 10.1111/odi.14273
11 Hashem AS , Issrani R , Elsayed TEE , et al. Topical hyaluronic acid in the management of oral lichen planus: A comparative study[J]. J Investig Clin Dent, 2019, 10 (2): e12385.
doi: 10.1111/jicd.12385
12 Vilar-Villanueva M , Gándara-Vila P , Blanco-Aguilera E , et al. Psychological disorders and quality of life in oral lichen planus patients and a control group[J]. Oral Dis, 2019, 25 (6): 1645- 1651.
doi: 10.1111/odi.13106
13 中华口腔医学会口腔黏膜病专业委员会. 口腔扁平苔藓(萎缩型、糜烂型)疗效评价标准(试行)[J]. 中华口腔医学杂志, 2005, 40 (2): 92- 93.
doi: 10.3760/j.issn:1002-0098.2005.02.002
14 Bindakhil M , Akintoye S , Corby P , et al. Influence of topical corticosteroids on malignant transformation of oral lichen planus[J]. J Oral Pathol Med, 2022, 51 (2): 188- 193.
doi: 10.1111/jop.13257
15 Chung HS , Kim Y , Oh SJ , et al. A synthetic compound, 4-acetyl-3-methyl-6-(3, 4, 5-trimethoxyphenyl)pyrano[3, 4-c]pyran-1, 8-dione, ameliorates ovalbumin-induced asthma[J]. Bioorg Med Chem, 2013, 21 (21): 6359- 6365.
doi: 10.1016/j.bmc.2013.08.045
16 Chen YT , Li J , Chang JN , et al. Transcriptomic analysis of world trade center particulate matter-induced pulmonary inflammation and drug treatments[J]. Environ Int, 2023, 177, 108027.
doi: 10.1016/j.envint.2023.108027
17 Matos Leitão M , Euclides Silva-Filho S , Arena AC , et al. Antinociceptive and anti-inflammatory properties of aqueous extract obtained from serjania marginata casar leaves[J]. J Ethnopharmacol, 2023, 304, 116018.
18 Valdez R , Cavinder CA , Varner DD , et al. Dexamethasone downregulates expression of several genes encoding orphan nuclear receptors that are important to steroidogenesis in stallion testes[J]. J Biochem Mol Toxicol, 2019, 33 (6): e22309.
doi: 10.1002/jbt.22309
19 Paulusová V , Laco J , Drízhal I , et al. Expression of matrix metalloproteinase 9 in patients with oral lichen planus[J]. Acta Medica (Hradec Kralove), 2012, 55 (1): 23- 26.
doi: 10.14712/18059694.2015.70
20 Wang H , Guan X , Luo Z , et al. The association and potentially destructive role of Th9/IL-9 is synergistic with Th17 cells by elevating mmp9 production in local lesions of oral lichen planus[J]. J Oral Pathol Med, 2018, 47 (4): 425- 433.
21 Kylmäniemi M , Oikarinen A , Oikarinen K , et al. Effects of dexamethasone and cell proliferation on the expression of matrix metalloproteinases in human mucosal normal and malignant cells[J]. J Dent Res, 1996, 75 (3): 919- 926.
22 Villa A , Sankar V , Bassani G , et al. Dexamethasone solution and dexamethasone in mucolox for the treatment of oral lichen planus: A preliminary study[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2020, 129 (6): 585- 590.
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[3] . [J]. Journal of Peking University(Health Sciences), 2002, 34(2): 112 -116 .
[4] . [J]. Journal of Peking University(Health Sciences), 2002, 34(5): 431 -433 .
[5] . [J]. Journal of Peking University(Health Sciences), 2008, 40(2): 214 -218 .
[6] . [J]. Journal of Peking University(Health Sciences), 2008, 40(5): 459 -464 .
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[8] . [J]. Journal of Peking University(Health Sciences), 2008, 40(5): 486 -488 .
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