Journal of Oral Pathology & Medicine最新文献

Introduction: Dysregulated expression of urokinase-type plasminogen activator (PLAU), a serine protease, is frequently associated with various cancers. However, in oral squamous cell carcinoma (OSCC), the specific biological functions and mechanisms of action of PLAU remain unclear.

Methods: Western blot (WB) analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of PLAU in oral squamous cell carcinoma; Flow cytometry was used to assess changes in OSCC cell cycle and apoptosis following PLAU knockdown. Transwell assays were conducted to evaluate alterations in cell invasion and migration after PLAU knockdown. LinkedOmics database was employed to analyze the correlation between PLAU and TGF-β1.

Results: Our study using GEPIA2 dataset analysis and WB experiments revealed that PLAU expression was upregulated in HNSC tissues and OSCC cell lines and was significantly associated with overall survival in patients. Furthermore, the invasive and migratory abilities of UM1 cells were significantly reduced following PLAU knockdown, as demonstrated by scratch assays and Transwell migration assays. Subsequently, Western blot analysis revealed that PLAU knockdown effectively inhibited the epithelial-mesenchymal transition (EMT) process. Meanwhile, LinkedOmics database analysis revealed a significant positive correlation between TGF-β1 and PLAU. Further investigations demonstrated that TGF-β1 induces PLAU upregulation, which subsequently promotes the migration, invasion, and EMT process in OSCC cells. Conversely, PLAU knockdown abrogates these TGF-β1-mediated effects.

Conclusion: PLAU acts as a key oncogenic driver in OSCC and may serve as a potential diagnostic and prognostic biomarker. More importantly, the TGF-β1-PLAU axis may offer new therapeutic targets for OSCC treatment.

Background: Cystadenoma of the salivary glands (CSG) is a rare benign, multicystic neoplasm, representing approximately 1%-4.7% of all benign salivary gland tumors. This study aimed to systematically review the clinicopathological data reported on case reports and case series of CSG.

Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Comprehensive searches were performed across PubMed, Web of Science, Scopus, and Embase electronic databases.

Results: A total of 81 studies were included, encompassing 126 cases of CSG. A slight female predominance was observed (54.91%), with a mean patient age of 54.2 ± 21.5 years. The median lesion size was 1.4 ± 1.6 cm. The parotid gland was the most affected site (23.47%). Most cases were asymptomatic (86.58%), and nodular presentation was noted in 70.96%. Mucocele was the most suspected clinical diagnosis. Histopathologically, the papillary subtype was predominant (67.03%), with oncocytic cells prevailing, followed by columnar and cuboidal cell types. Of the 57 cases with available data on growth pattern, 38 were multicystic and 19 unicystic. Immunohistochemical analysis frequently involved the use of p63, MUC4, MUC1, and CK7. All cases were managed surgically, with a recurrence rate of 6.25%. The median follow-up period was 12.1 ± 23.2 months.

Conclusion: CSG is a rare benign tumor that predominantly affects the parotid gland in female patients, typically presenting as a multicystic lesion. Surgical excision remains the treatment of choice, with a generally favorable prognosis.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common subtypes of head and neck squamous cell carcinoma (HNSCC), characterized by high recurrence rates and poor prognosis. SPOCD1 has been identified as a facilitator of tumor progression in several cancers; however, its regulatory role in OSCC has not yet been reported.

Design: Using The Cancer Genome Atlas (TCGA) database, we examined SPOCD1 expression in HNSCC tissues. mRNA and protein levels of SPOCD1 in OSCC cells were assessed by RT-qPCR and western blotting. The effects of SPOCD1 on cell proliferation, invasion, and migration were evaluated using CCK-8, colony formation, wound healing, and Transwell assays. Western blotting was performed to confirm the impact of SPOCD1 on the PI3K/Akt/mTOR pathway. The influence of SPOCD1 on tumor growth was further investigated in vivo.

Results: Analysis of the TCGA database revealed that SPOCD1 expression was upregulated in HNSCC tissues, consistent with our experimental data showing increased SPOCD1 expression in OSCC cells. Inhibition of SPOCD1 suppressed cell proliferation, while its overexpression enhanced proliferation. Similarly, SPOCD1 knockdown reduced migration and invasion, whereas overexpression promoted these processes. In addition, SPOCD1 was found to activate the PI3K/Akt/mTOR pathway. In vivo experiments further demonstrated that SPOCD1 significantly accelerated tumor growth.

Conclusion: This study demonstrates that SPOCD1 promotes OSCC growth and metastasis by activating the PI3K/Akt/mTOR pathway, indicating that SPOCD1 may represent a potential therapeutic target for OSCC treatment.

Background: Sclerosing odontogenic carcinoma (SOC) is a rare intraosseous neoplasm defined by the World Health Organization as a locally aggressive tumor with "no metastatic potential".

Objective: This review provides a critical evaluation of the biological behavior, clinicopathologic features, and clinical management of SOC cases, with a particular focus on neural invasion and cellular proliferation scores.

Methods: A comprehensive literature was performed using the Pubmed and Scopus databases to identify all published English-language reports of SOC.

Results: The analysis of 22 reported cases revealed that SOC predominantly affects the mandible in middle-aged adults, typically presenting as a radiolucent lesion associated with cortical resorption. Histopathologically, perineural invasion was identified in 77.3% of cases and revealed a wide range of Ki-67 expression (1%-%30).

Conclusion: This challenging entity exhibits a spectrum of malignant potential, and the current classification standard of "no metastatic potential" requires revision. In cases exhibiting diverse biological behaviors, the Ki-67 proliferation score can be used an ancillary marker for risk stratification; higher rates (e.g., > 10%-15%) may be associated with aggressive local invasion and metastatic events. Further molecular studies on aggressive "metastatic" cases are imperative to allow for identification of definitive markers that can establish SOC as a distinct entity and provide a rational basis for risk assessment and treatment.

Background: Mucosal melanomas of the head and neck are rare and often diagnosed in the advanced stage. This study examines the incidence, survival and histology of mucosal melanoma compared to its cutaneous counterpart.

Methods: This register-based cohort study reviews head and neck melanomas at Helsinki University Hospital, Finland, from 2002 to 2023.

Results: A total of 56 patients with mucosal and 714 with cutaneous melanoma were reviewed. The incidence of head and neck mucosal melanoma in the region was 1.55/million/year. The most common sites for mucosal melanomas were the nose and paranasal sinuses. Mucosal melanoma was more common in women, whereas cutaneous melanoma was more common in men (p > 0.05). A significant difference emerged in mortality between mucosal and cutaneous melanoma, as 5-year survival was only 12.0% in the mucosal melanoma group compared with 60.3% in the cutaneous melanoma group.

Conclusions: Mucosal melanoma is a highly aggressive malignancy with poor survival; thus, prompt diagnosis is essential.

Background: Chronic mechanical irritation (CMI) has been proposed as a risk factor for oral cancer. Epigenetic alterations, particularly methylation, are early events in carcinogenesis, and it has been proposed that they can be prompted by CMI. Thus, the aim of this study was to describe p16 and MGMT methylation in chronic traumatic ulcer (CTU).

Methods: A case-control split-mouth study was performed. Two samples per individual (N = 27) were taken using exfoliative cytology using a split-mouth design, one from the CTU and the other from a contralateral site of clinically normal mucosa. DNA was extracted and bisulfite-treated, and specific sites at the promoter region of p16 and MGMT genes were amplified by qPCR using validated primers. Then, the PCR product was sequenced. The statistical analysis was performed by McNemar and the Chi-square test.

Results: Patients had a mean age of 59.1 years. CTU showed higher methylation than control sites for both p16 (85% vs. 20%, p < 0.0001) and MGMT (80% vs. 24%, p < 0.0005).

Conclusion: Oral mucosa subjected to continuous exposure to CMI is associated with increased methylation of p16 and MGMT. Proper management of mechanical injury factors could be an important measure for OSCC prevention. In CMI, exfoliative cytology and the split-mouth design could be useful tools to study biomarkers. However, the role of CMI in oral carcinogenesis needs more evidence focusing on the biological phenomenon.

Aim: This retrospective study investigates the interplay between epithelial-mesenchymal transition (EMT) and immune response within the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC).

Methodology: Immunohistochemistry was conducted on OSCC specimens to evaluate the expression of podoplanin (PDP), E-cadherin (CDH1), vimentin (VIM), fibronectin (FN), tenascin-C (TNC), and vascular endothelial growth factor (VEGF). Cancer-associated fibroblasts (CAFs) were identified by alpha-smooth muscle actin (α-SMA), and immune cells were quantified using CD66b for neutrophils and CD8 for T lymphocytes.

Results: Higher α-SMA and moderate-to-strong VEGF expression were associated with reduced CDH1 and increased VIM and PDP expression (p < 0.05), indicating an EMT-like phenotype. Cases with elevated PDP-also linked to high α-SMA-showed increased CD66b⁺ cell density (p = 0.072). VEGF expression additionally correlated with greater tumor thickness and depth of invasion (p = 0.059). Strong TNC expression was associated with reduced CD8⁺ T-cell infiltration in the tumor centre and increased CD66b⁺ neutrophils (p < 0.046). Strong FN expression was linked to a higher neutrophil-to-lymphocyte ratio (p = 0.031). Elevated CD66b⁺ cell counts and a higher neutrophil-to-lymphocyte ratio were both significantly associated with poorer overall survival (p < 0.015).

Conclusion: These exploratory findings suggest that CAFs serve not only as a marker of stromal activation but may also contribute to immunomodulation and invasive tumor phenotype.

Purpose: Doxorubicin (DOX) is a widely used chemotherapy drug, but its severe toxic effects, including inflammation and taste disturbances, limit its clinical use. This study examined the protective effects of vitamin D on DOX-induced changes in tongue tissue and systemic inflammation in rats.

Methods: Twenty-eight adult male Wistar Albino rats (10-12 weeks old) were divided into four groups: Control, DOX, Vitamin D 5000 + DOX, and Vitamin D 60 000 + DOX. Vitamin D3 was administered intraperitoneally either daily (5000 IU/kg) or 3 days a week (60 000 IU/kg) for 21 days. DOX (18 mg/kg, intraperitoneally) was administered on days 19-21. Tongue tissues were analyzed for angiotensin-converting enzyme 2 (ACE2) expression via immunohistochemistry, and serum cytokine levels (TNF-α, IL-1β, and IL-6) were measured using enzyme-linked immunosorbent assay (ELISA).

Results: DOX treatment significantly increased ACE2 expression in tongue tissue compared with controls (p < 0.001), accompanied by elevated serum inflammatory cytokine levels and reduced body weight. Vitamin D supplementation significantly attenuated DOX-induced ACE2 upregulation and inflammatory cytokine elevations (p < 0.05). However, no clear dose-dependent difference was observed between the two vitamin D regimens, as ACE2 expression did not differ significantly between the 5000 IU/kg and 60 000 IU/kg groups.

Conclusion: DOX administration is associated with increased ACE2 expression in tongue tissue and systemic inflammation in a rat model. Vitamin D supplementation mitigates these DOX-induced alterations; however, within the tested dose range, no additional benefit of the higher vitamin D dose was demonstrated. These findings suggest a potential modulatory role of vitamin D on chemotherapy-associated inflammatory and molecular changes, while highlighting the need for further mechanistic and functional studies.

Background: Oral lichen planus (OLP) is a chronic T-cell-mediated immune disease of unknown aetiology. MicroRNA (miRNAs) are short non-coding RNAs capable of regulating mRNA and may have roles in T-cell-related diseases. The aim of this study was to investigate the profile of miRNAs in OLP patients and its interaction with potential target genes.

Methods: Total RNA was extracted from fresh frozen biopsies from 24 patients with OLP and 8 control patients. The NanoString Counter Analysis System was used to analyse total RNA samples for differential miRNA expression. NanoString expression was confirmed by RT-qPCR analysis. Genes potentially targeted by upregulated and downregulated miRNAs were identified, and RT-qPCR was employed to investigate the expression of target genes in OLP and controls. Probability values < 0.05 were considered statistically significant.

Results: NanoString analysis showed that eight miRNAs, miR-155, miR-146a, miR-3195, miR-342, miR-4516, miR-21, miR-29a and miR-193 were upregulated in OLP tissues. Contrarily, the other eight miRNAs, miR-221, miR-200b, miR-149, miR-205, miR-27b, miR-95, miR-127b, miR-95, miR-206 were downregulated in OLP tissues. NanoString findings have been confirmed by RT-qPCR results for four upregulated miRNAs, miR-155, miR-146a, miR-29a and miR-342, and one downregulated miRNA, namely miR-205. The expression of two target genes, namely MYC for miR-29a and interleukin-24 (IL-24) for miR-205, was found to negatively correlate with the respective miRNA. This suggests that MYC and IL-24 could be regulated by the above miRNAs in OLP.

Conclusions: The work presented in this study suggests that miRNAs could be involved in both the immunopathogenesis and malignant transformation of OLP.