Dysregulation of TCONS_00006091 contributes to the elevated risk of oral squamous cell carcinoma by upregulating SNAI1, IRS and HMGA2.

In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study.

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.

Downregulation of salivary miR-3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus.

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

Development of an immune-related diagnostic predictive model for oral lichen planus.

Oral lichen planus (OLP) was a chronic inflammatory disease of unknown etiology with a 1.4% chance of progressing to malignancy. However, it has been suggested in several studies that immune system disorders played a dominant role in the onset and progression of OLP. Therefore, this experiment aimed to develop a diagnostic prediction model for OLP based on immunopathogenesis to achieve early diagnosis and treatment and prevent cancer. In this study, 2 publicly available OLP datasets from the gene expression omnibus database were filtered. In the experimental group (GSE52130), the level of immune cell infiltration was assessed using MCPcounter and ssGSEA algorithms. Subsequently, differential expression analysis and gene set enrichment analysis were performed between the OLP and control groups. The resulting differentially expressed genes were intersected with immunologically relevant genes provided on the immunology database and analysis portal database (ImmPort) website to obtain differentially expressed immunologically relevant genes (DEIRGs). Furthermore, the gene ontology and kyoto encyclopedia of genes and genomes analyses were carried out. Finally, protein-protein interaction network and least absolute shrinkage and selection operator regression analyses constructed a model for OLP. Receiver operating characteristic curves for the experimental and validation datasets (GSE38616) were plotted separately to validate the model's credibility. In addition, real-time quantitative PCR experiment was performed to verify the expression level of the diagnostic genes. Immune cell infiltration analysis revealed a more significant degree of inflammatory infiltration in the OLP group compared to the control group. In addition, the gene set enrichment analysis results were mainly associated with keratinization, antibacterial and immune responses, etc. A total of 774 differentially expressed genes was obtained according to the screening criteria, of which 65 were differentially expressed immunologically relevant genes. Ultimately, an immune-related diagnostic prediction model for OLP, which was composed of 5 hub genes (BST2, RNASEL, PI3, DEFB4A, CX3CL1), was identified. The verification results showed that the model has good diagnostic ability. There was a significant correlation between the 5 hub diagnostic biomarkers and immune infiltrating cells. The development of this model gave a novel insight into the early diagnosis of OLP.

Immunophenotypic and Gene Expression Analyses of the Inflammatory Microenvironment in High-Grade Oral Epithelial Dysplasia and Oral Lichen Planus.

BACKGROUND: Oral lichen planus (OLP) and oral epithelial dysplasia (OED) present diagnostic challenges due to clinical and histologic overlap. This study explores the immune microenvironment in OED, hypothesizing that immune signatures could aid in diagnostic differentiation and predict malignant transformation. METHODS: Tissue samples from OED and OLP cases were analyzed using immunofluorescence/immunohistochemistry (IF/IHC) for CD4, CD8, CD163/STAT1, and PD-1/PDL-1 expression. RNA-sequencing was performed on the samples, and data was subjected to CIBERSORTx analysis for immune cell composition. Gene Ontology analysis on the immune differentially expressed genes was also conducted. RESULTS: In OED, CD8 + T-cells infiltrated dysplastic epithelium, correlating with dysplasia severity. CD4 + lymphocytes increased in the basal layer. STAT1/CD163 + macrophages correlated with CD4 + intraepithelial distribution. PD-1/PDL-1 expression varied. IF/IHC analysis revealed differential immune cell composition between OED and OLP. RNA-sequencing identified upregulated genes associated with cytotoxic response and immunosurveillance in OED. Downregulated genes were linked to signaling, immune cell recruitment, and tumor suppression. CONCLUSIONS: The immune microenvironment distinguishes OED and OLP, suggesting diagnostic potential. Upregulated genes indicate cytotoxic immune response in OED. Downregulation of TRADD, CX3CL1, and ILI24 implies dysregulation in TNFR1 signaling, immune recruitment, and tumor suppression. This study contributes to the foundation for understanding immune interactions in OED and OLP, offering insights into future objective diagnostic avenues.

Inflammatory cytokines and oral lichen planus: a Mendelian randomization study.

Background: Inflammatory cytokines have long been considered closely related to the development of oral lichen planus (OLP), and we further explored the causal relationship between the two by Mendelian randomization (MR) method. Methods: We performed bidirectional MR analyses by large genome-wide association studies (GWAS). The data included a large-scale OLP dataset, as well as datasets of 41 inflammatory cytokines. All data were obtained from the University of Bristol database, which includes 41 inflammatory cytokines, and the GWAS Catalog database, which includes 91 inflammatory cytokines. OLP data were obtained from the Finngen database, which includes 6411 cases and 405770 healthy controls. We used the inverse variance weighted (IVW) method, MR-Egger method, weighted median method, simple mode method and weighted mode method to analyze the causal relationship between inflammatory cytokines and OLP, and we also combined with sensitivity analysis to further verify the robustness of the results. We performed a meta-analysis of positive or potentially positive results for the same genes to confirm the reliability of the final results. Results: We primarily used the IVW analysis method, corrected using the Benjamin Hochberg (BH) method. When p<0.00038 (0.05/132), the results are significantly causal; when 0.00038

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

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.

Clinical value and potential circulating of miR-99a as tumor suppressor biomarker in serum of oral squamous cell carcinoma and erosive atrophic lichen planus.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasms that consist of more over 90% of oral cancers. It was demonstrated that erosive atrophic oral lichen planus (OLP) has potential of malignancy transformation into OSCC. The microRNAs are non-coding regulator sequences involved in cancer process. The miR-99a involve in growth, proliferation, migration, invasion, and metastasis of tumor cells. Therefore, we evaluated miR-99a expression in serum of OSCC and erosive atrophic OLP patients in comparison to healthy control individuals to more investigate about level of miR-99a expression in potential premalignant disorder (erosive atrophic OLP) in comparison to malignant transformation form (OSCC). Gene ontology (GO) and pathway analyses were performed to better understand the importance of miR-99a in OSCC. MATERIALS AND METHODS: In this cross-sectional study, total 90 serum samples from OSCC patients (n = 30), erosive atrophic OLP (n = 30) and healthy control individuals (n = 30) were collected, and then evaluated for miR-99a expression by qPCR. Pathway analysis and protein-protein interaction were done using STRING (v: 12.0), and (GO) terms and related genes were extracted from the GO online search tool. The statistical analysis was evaluated by Kruskal Wallis, Chi-Square, Kruskal Wallis, Spearman and Mann-Whitney tests. The p-value less than 0.05 was considered statistically significant. RESULTS: miR-99a expression down regulated in OSCC in comparison to erosive atrophic OLP and control groups (p < 0.05). The miR-99a up regulated in grade I more than grades II and III (p < 0.05). We showed upregulation of miR-99a in early stage more than advanced stage (p < 0.05). Expression of miR-99a reduced accordance to the increasing of tumor size and lymph involvement levels (p < 0.05). The 165 determined targets were classified into three domains. The most significant enrichment in biological processes, cellular components, and molecular functions was in the cellular nitrogen compound biosynthetic process, cytosolic ribosome, and protein binding, respectively. CONCLUSIONS: We highlighted tumor suppressive role of miR-99a in OSCC patients. It seems that miR-99a can be considered a valuable biomarker for the early diagnosis of erosive atrophic OLP before transformation. CLINICAL RELEVANCE: Our results may help to better understand the prognostic factor for oral squamous cell carcinoma to evaluate survival and subsequent tumor development. And it may also help to understand the pathogenesis of OSCC.

Unveiling the Potential of Serum MiR-483-5p: A Promising Diagnostic and Prognostic Biomarker in OLP and OSCC Patients by In silico Analysis of Differential Gene Expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.

The expression of p53, ki67 and COX-2 in erosive-type oral lichen planus.

Oral lichen planus is a chronic inflammatory disease that affects the oral mucosa and may undergo malignant changes, which can be reflected in the expression of specific proteins that are responsible for maintaining cellular mitosis and apoptosis. The study aimed to investigate the expression of p53, ki67, and COX-2 in erosive lichen planus using immunohistochemistry to correlate these findings with the histological aspects of the disease. Thirty-three biopsies of erosive lichen planus were collected and diagnosed based on histological and clinical criteria. The blocks were processed for immunohistochemistry to assess p53, ki67, and COX-2 expression in the basal layer, suprabasal, and inflammatory infiltrate respectively. The histological analysis of the samples showed no dysplasia or metastasis. P53 stained positively in 80% of the samples, while ki67 was positive in all the cases, ranging from 5% to 85% positivity. COX-2 expression ranged from 0-50% positivity. The highest expression of p53 was observed in 8 cases (24.2%), with a maximum of 5%, and ki67 exhibited the highest expression of 90% in 3 cases (9.1%). COX-2 was negative in 27 cases (81.8%) and positive in 6 cases (18.1%), with the highest expression at 50% in 1 case and 10 % positivity in 4 cases (12.1%). In our study, the markers p53, ki67, and COX-2 proved to be useful for detecting the proliferative, inflammatory, and physiologic states of the keratinocytes. However, they did not demonstrate utility in detecting any malignant transformation.

Non-Coding RNAs as Potential Targets for Diagnosis and Treatment of Oral Lichen Planus: A Narrative Review.

Oral lichen planus (OLP) is a chronic inflammatory disease that is characterized by the infiltration of T cells into the oral mucosa, causing the apoptosis of basal keratinocytes. OLP is a multifactorial disease of unknown etiology and is not solely caused by the malfunction of a single key gene but rather by various intracellular and extracellular factors. Non-coding RNAs play a critical role in immunological homeostasis and inflammatory response and are found in all cell types and bodily fluids, and their expression is closely regulated to preserve normal physiologies. The dysregulation of non-coding RNAs may be highly implicated in the onset and progression of diverse inflammatory disorders, including OLP. This narrative review summarizes the role of non-coding RNAs in molecular and cellular changes in the oral epithelium during OLP pathogenesis.

METTL14-upregulated miR-6858 triggers cell apoptosis in keratinocytes of oral lichen planus through decreasing GSDMC.

Oral lichen planus (OLP), a chronic inflammatory disorder, is characterized by the massive cell apoptosis in the keratinocytes of oral mucosa. However, the mechanism responsible for triggering oral keratinocyte apoptosis is not fully explained. Here, we identify that Gasdermin C (GSDMC) downregulation contributes to apoptosis in human oral keratinocytes. Mechanistically, we describe that activated nuclear factor kappa B (NF-κB) pathway induces overexpression of methyltransferase-like 14 (METTL14), which increases N6-adenosine methylation (m6A) levels in the epithelial layer of OLP. m6A modification is capable of regulating primary miR-6858 processing and alternative splicing, leading to miR-6858 increases. miR-6858 can bind and promote GSDMC mRNA degradation. Forced expression of GSDMC is able to rescue cell apoptosis in human oral keratinocyte models resembling OLP. Collectively, our data unveil that m6A modification regulates miR-6858 production to decrease GSDMC expression and to trigger keratinocyte apoptosis in the context of OLP.

CircHLA-C: A significantly upregulated circRNA co-existing in oral leukoplakia and oral lichen planus.

BACKGROUND: Oral leukoplakia (OLK) and oral lichen planus (OLP) are common precancerous lesions of the oral mucosa. The role of circular RNAs (circRNAs) in OLK and OLP is unclear. The aim of this study was to evaluate the circRNA expression profiles of OLK and OLP, and further explore the potential role of circRNAs in the pathogenesis of these two diseases. METHODS: High throughput sequencing technology was performed to detect the differentially expressed circRNA in OLK (n = 6), OLP (n = 6), oral squamous cell carcinoma (n = 6), and normal oral mucosa tissues (n = 6). Expression of selected circRNAs was validated by qRT-PCR, enzyme tolerance assay, and Sanger sequencing. Expanded sample size validation was done in 20 tissue pairs. The biological processes and signal pathways involved in differential circRNA were analyzed by GO and KEGG enrichment. TargetScan and MiRanda were used to predict miRNAs downstream of circRNA and draw competitive endogenous RNA network diagram. RESULTS: Forty-nine circRNAs were significantly altered in OLK and OLP, including 30 upregulated and 19 downregulated circRNAs. The five selected circRNAs were validated by qRT-PCR, Sanger sequencing, and RNase R assay. GO and KEGG analyses indicated that the upregulated circHLA-C may be involved in the biological process of immune function of OLK and OLP. Bioinformatics analysis indicated that circHLA-C may be involved in the progression of OLK and OLP as a ceRNA. In validation with expanded sample size, PCR results showed that circHLA-C expression was significantly upregulated in OLK and OLP. ROC analysis indicated that circHLA-C has potential diagnostic value with good accuracy and specificity. CONCLUSION: Our study revealed that circHLA-C is the most significantly upregulated circRNA co-existing in OLK and OLP, and we preliminarily discuss the role of circHLA-C in the etiopathogenesis and progression of OLK and OLP.

CD8 + T-cell marker genes reveal different immune subtypes of oral lichen planus by integrating single-cell RNA-seq and bulk RNA-sequencing.

BACKGROUND: Oral lichen planus (OLP) is a local autoimmune disease induced by T-cell dysfunction that frequently affects middle-aged or elderly people, with a higher prevalence in women. CD8 + T cells, also known as killer T cells, play an important role in the progression and persistence of OLP. In order to identify different OLP subtypes associated with CD8 + T cell pathogenesis, consensus clustering was used. METHODS: In this study, we preprocessed and downscaled the OLP single-cell dataset GSE211630 cohort downloaded from Gene Expression Omnibus (GEO) to finally obtain the marker genes of CD8 + T cells. Based on the expression of marker genes, we classified OLP patients into CMGs subtypes using unsupervised clustering analysis. The gene expression profiles were analyzed by WGCNA using the "WGCNA" R package based on the clinical disease traits and typing results, and 108 CD8 + T-cell related OLP pathogenicity-related genes were obtained from the intersection. Patients were once again classified into gene subtypes based on intersection gene expression using unsupervised clustering analysis. RESULTS: After obtaining the intersecting genes of CD8 + T cells related to pathogenesis, OLP patients can be precisely classified into two different subtypes based on unsupervised clustering analysis, and subtype B has better immune infiltration results, providing clinicians with a reference for personalized treatment. CONCLUSIONS: Classification of OLP into different subtypes improve our current understanding of the underlying pathogenesis of OLP and provides new insights for future studies.

Salivary level of microRNA-146a and microRNA-155 biomarkers in patients with oral lichen planus versus oral squamous cell carcinoma.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa, which has potential for malignant transformation. MicroRNAs play an important role in immunopathogenesis of OLP, and may be used for prediction of its malignant transformation. This study aimed to assess the salivary level of microRNA-146a and microRNA-155 biomarkers in patients with OLP and oral squamous cell carcinoma (OSCC). METHODS: In this case-control study, unstimulated saliva samples were collected from 60 patients, including 15 patients with dysplastic OLP, 15 OLP patients without dysplasia, 15 patients with OSCC, and 15 healthy controls according to the Navazesh technique. After RNA extraction, the expression of microRNA-146a and microRNA-155 was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). The data were analyzed by the Kruskal-Wallis and Dunn-Bonferroni tests. RESULTS: The difference in expression of microRNA-146a and microRNA-155 among the four groups was significant (P < 0.05). Pairwise comparisons of the groups showed significantly higher expression of microRNA-146a in OLP (P = 0.004) and dysplastic OLP (P = 0.046) patients compared with the control group. Up-regulation of this biomarker in OSCC patients was not significant compared with the control group (P = 0.076). Up-regulation of micro-RNA-155 was only significant in OLP group, compared with the control group (P = 0.009). No other significant differences were found (P > 0.05). CONCLUSION: Considering the altered expression of MicroRNA-146a and microRNA-155 in dysplastic OLP and OSCC, their altered expression may serve as an alarming sign of malignancy. However, further investigations are still required.

Single-cell immune profiling reveals immune responses in oral lichen planus.

Introduction: Oral lichen planus (OLP) is a common chronic inflammatory disorder of the oral mucosa with an unclear etiology. Several types of immune cells are involved in the pathogenesis of OLP. Methods: We used single-cell RNA sequencing and immune repertoire sequencing to characterize the mucosal immune microenvironment of OLP. The presence of tissue-resident memory CD8+ T cells are validated by multiplex immunofluorescence. Results: We generated a transcriptome atlas from four OLP biopsy samples and their paired peripheral blood mononuclear cells (PBMCs), and compared them with two healthy tissues and three healthy PBMCs samples. Our analysis revealed activated tissue-resident memory CD8+ T cells in OLP tissues. T cell receptor repertoires displayed apperant clonal expansion and preferrential gene pairing in OLP patients. Additionally, obvious BCR clonal expansion was observed in OLP lesions. Plasmacytoid dendritic cells, a subtype that can promote dendritic cell maturation and enhance lymphocyte cytotoxicity, were identified in OLP. Conventional dendritic cells and macrophages are also found to exhibit pro-inflammatory activity in OLP. Cell-cell communication analysis reveals that fibroblasts might promote the recruitment and extravasation of immune cells into connective tissue. Discussion: Our study provides insights into the immune ecosystem of OLP, serving as a valuable resource for precision diagnosis and therapy of OLP.

Is OLP potentially malignant? A clue from ZNF582 methylation.

OBJECTIVE: Whether oral lichen planus (OLP) was potentially malignant remains controversial. Here, we examined associations of ZNF582 methylation (ZNF582m ) with OLP lesions, dysplastic features and squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This is a case-control study. ZNF582m was evaluated in both lesion and adjacent normal sites of 42 dysplasia, 90 OSCC and 43 OLP patients, whereas ZNF582m was evaluated only in one mucosal site of 45 normal controls. High-risk habits affecting ZNF582m such as betel nut chewing and cigarette smoking were also compared in those groups. RESULTS: OLP lesions showed significantly lower ZNF582m than those of dysplasia and OSCC. At adjacent normal mucosa, ZNF582m increased from patients of OLP, dysplasia, to OSCC. In addition, ZNF582m at adjacent normal sites in OLP patients was comparable to normal mucosa in control group. Dysplasia/OSCC patients with high-risk habits exhibited significantly higher ZNF582m than those without high-risk habits. However, ZNF582m in OLP patients was not affected by those high-risk habits. CONCLUSIONS: OLP is unlikely to be potentially malignant based on ZNF582m levels. ZNF582m may also be a potential biomarker for distinguishing OLP from true dysplastic features and OSCC, and for monitoring the malignant transformation of OLP, potentially malignant disorders with dysplastic features and OSCC.

Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures.

To investigate similarities in the gene profile of Oral Lichen Planus and Oral Squamous Cell Carcinoma that may justify a carcinogenic potential, we analyzed the gene expression signatures of Oral Lichen Planus and Oral Squamous Cell Carcinoma in early and advanced stages. Based on gene expression data from public databases, we used a bioinformatics approach to compare expression profiles, estimate immune infiltrate composition, identify differentially and co-expressed genes, and propose putative therapeutic targets and associated drugs. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between Oral Lichen Planus and early and advanced Oral Squamous Cell Carcinoma, with the cornified envelope formation and antigen processing cross-presentation pathways in common between Oral Lichen Planus and early Oral Squamous Cell Carcinoma. Together, these results reveal that key tumor suppressors and oncogenes such as PI3, SPRR1B and KRT17, as well as genes associated with different immune processes such as CXCL13, HIF1A and IL1B are dysregulated in OLP.

Comparison of biomarker expression in oral lichen planus and oral lichenoid lesions.

BACKGROUND: Oral lichen planus (OLP) and oral lichenoid lesions (OLL) comprise a group of oral mucosal disorders that have similar clinical and histological features. OBJECTIVES: To compare the levels of investigated biomarkers in biopsied OLP and OLL, and to determine the pattern of biomarkers, which could be useful for the biological characterization of these 2 disorders. MATERIAL AND METHODS: A total of 56 biopsy specimens in 2 groups were analyzed in this study. One group consisted of 25 idiopathic OLP lesions, and the other included 31 OLL from patients treated with antihypertensive and cardiac medications. The expression of protein p53, topoisomerase I (topo I), heat shock protein 90 (HSP90), and E-cadherin was analyzed using immunohistochemistry. RESULTS: The p53 protein expression showed a trend to a positive correlation with topo I expression in the total sample (p = 0.067, R = 0.25). The p53 protein and HSP90 expression was higher in the OLL group compared to the OLP group, but the difference was not statistically significant. No association was found between topo I and E-cadherin expression for either the OLP or OLL group. CONCLUSIONS: The findings of this study suggest that the slightly higher protein p53 and HSP90 expression in the OLL group might be caused by the medications used. The slight association between p53 and topo I expression indicates that the cooperation between these proteins might be essential for the growth of OLP/OLL in general. We conclude that the overexpression of p53 protein and high expression of topo I found in both types of lesions might induce their biologically aggressive behavior.

Differential genotypes of TNF-α and IL-10 for immunological diagnosis in discoid lupus erythematosus and oral lichen planus: A narrative review.

Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians' understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.