Search Results (282)

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 patients, while variants in PD-1 (rs36084323), PD-L1 (rs822336, rs4143815, copy number variation), FOXP3 (rs3761548, rs2232365), and miR-155 (rs767649) were assessed in 134 patients. Expression data were validated using the TCGA cohort of 222 HPV-negative OSCC cases. Low FOXP3 expression was significantly associated with tumor stage (MMA: p = 0.028, TCGA: p = 0.025) and poor overall survival (MMA: p = 0.0004, TCGA: p = 0.019) in both cohorts. Declining FOXP3 expression correlated with advancing tumor stages, and low FOXP3 expression was significantly associated with poor survival in advanced stage III–IV tumors (MMA: p = 0.001, TCGA: p = 0.015), but not early-stage tumors. High miR-155 expression was associated with recurrence (p = 0.002) and poor survival in the MMA (p = 0.007), but not TCGA cohort. MiR-155 rs767649 was associated with alcohol consumption (p = 0.018). These findings point to FOXP3 and miR-155 as potential prognostic biomarkers for HPV-negative OSCC. Stage-specific FOXP3 expression suggests a dynamic immunoregulatory role, with implications for optimizing immunotherapy timing. Further studies are warranted to resolve cellular context and stage-adapted immune interventions in HPV-negative OSCC. Full article

Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

Oral squamous cell carcinoma (OSCC) remains a significant global health challenge, representing 90% of oral malignancies. Despite therapeutic advances, patient outcomes remain poor, highlighting the need for novel prognostic biomarkers and treatment targets. We investigated the expression patterns of NTRK genes and their corresponding proteins (TrkA, TrkB, and TrkC) in OSCC, analyzing their relationships with clinical outcomes and potential as therapeutic targets. We examined 93 OSCC tissue samples using immunohistochemistry and quantitative real-time PCR. Protein expression was quantified using the H-score method. We analyzed correlations between Trk expression, clinicopathological parameters, and 2-year survival rates using chi-square tests, Mann–Whitney U tests, and Kaplan–Meier survival analysis. TrkA showed near-universal expression (97.8%—91 patients) in OSCC samples, with high expression levels significantly correlating with lower tumor grade (p = 0.014) and improved 2-year survival (p = 0.011). While TrkB and TrkC were expressed in 65.5% and 84.9% of cases, respectively, neither showed significant associations with clinical parameters. NTRK2 and NTRK3 mRNA levels demonstrated a strong positive correlation (R = 0.64, p = 0.002), suggesting coordinated regulation. Our findings establish TrkA as a promising positive prognostic marker in OSCC, warranting investigation as a therapeutic target. The strong correlation between NTRK2 and NTRK3 expression suggests shared regulatory mechanisms in OSCC pathogenesis. Further studies with larger cohorts and longer follow-up periods are needed to validate these findings and explore their therapeutic implications. Full article

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor prognosis, largely due to its high metastatic potential and resistance to conventional therapies. Recent advances in cancer biology have underscored the significance of regulated cell death pathways, including apoptosis, autophagic cell death (ACD), necroptosis, pyroptosis, and ferroptosis, in modulating tumor progression and therapeutic responses. This review provides the current insights into the molecular mechanisms underlying these cell death pathways and explores their therapeutic relevance in OSCC. Restoration of apoptosis using BH3 mimetics, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonists, and p53 reactivators shows promise for sensitizing OSCC cells to treatment. Autophagy plays context-dependent roles in cancer, acting as a tumor suppressor during early carcinogenesis by maintaining cellular homeostasis, and as a tumor promoter in established tumors by supporting cancer cell survival under stress. Targeting necroptosis and pyroptosis has emerged as a novel strategy for inducing cancer cell death, with compounds such as acetylshikonin and okanin demonstrating antitumor effects. Additionally, the induction of ferroptosis via lipid peroxidation and glutathione peroxidase 4 (GPX4) inhibition offers a promising avenue for overcoming drug resistance, with agents such as quercetin and trifluoperazine exhibiting preclinical success. Integration of these therapeutic approaches may enhance the OSCC treatment efficacy, reduce chemoresistance, and provide novel prognostic biomarkers for clinical management. Future studies should focus on optimizing combinatorial strategies that effectively leverage these pathways to improve OSCC patient outcomes. Full article

(1) Background: Oral cancer (OC) is one of the most frequently diagnosed human cancers and remains a challenge for biologists and clinicians. More than 90% of OC cases are squamous cell carcinomas (OSCCs). Despite the use of modern diagnostic and prognostic methods, the 5-year survival rate remains unsatisfactory due to the late diagnosis of the neoplastic process and its resistance to treatment. This comprehensive review aims to present the latest literature data on the use and effectiveness of saliva as a non-invasive biomarker in patients with oral cancer. (2) Methods: The article reviews the current literature on the use of salivary omics biomarkers as an effective method in diagnosing and modifying treatment in patients with OSCC; the research corpus was acquired from the PubMed/Google/Scopus/Cochrane Library/Web of Science databases in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA 2020) guidelines. (3) Results: The identification of salivary omics biomarkers involved in carcinogenesis and neoplastic transformation may be a potential alternative to traditional invasive diagnostic methods. Saliva, being both an abundant reservoir of organic and inorganic components derived from epithelial cells as well as a cell-free environment, is becoming an interesting diagnostic material for studies in the field of proteomics, genomics, metagenomics, and metabolomics. (4) Conclusions: Saliva-based analysis is a modern and promising method for the early diagnosis and improvement of treatment outcomes in patients with OSCC and oral potentially malignant disorders (OPMDs), with high diagnostic, therapeutic, and prognostic potential. Full article

This study aims to investigate the prognostic impact of cellular components of the tumor microenvironment (TME), analyzed through immunohistochemistry, in oral squamous cell carcinoma (OSCC). This review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Web of Science, ScienceDirect, Scopus, and Google Scholar. After applying the study criteria, 59 articles were included, involving the analysis of cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. It was found that TME rich in α-SMA-positive CAFs, tumor-associated macrophages, and dendritic cells contribute to the invasion and progression of OSCC, resulting in a poorer prognosis. In contrast, the presence of high amounts of NK CD57⁺ cells, CD8⁺/CD45RO⁺ T cells, and PNAd⁺ endothelial cells are associated with anti-tumor immune responses in OSCC and improved survival rates. CD3⁺ and CD4⁺ T cells, Treg cells, B cells, and mast cells have shown little to no evidence of prognostic utility. Several stromal components of TME were found to have a strong impact on the aggressiveness of OSCC, reaffirming the potential use of these biomarkers as prognostic tools and therapeutic targets. Full article

Background: Eighty-five percent of peri-implant malignancies are oral squamous cell carcinomas (OSCCs), and most of them are misdiagnosed as peri-implantitis because of their clinical and radiological presentation; few studies have focused on addressing and solving the diagnostic issues related to peri-implant OSCCs. Objectives: The study aimed to describe the clinicopathological features of peri-implant OSCCs and to report the staging issues related to the diagnosis of these lesions. Methods: This retrospective cohort study included patients who received a diagnosis of and treatment for peri-implant OSCCs at the Unit of Dentistry of the “Aldo Moro” University of Bari (Italy) from 2018 to 2024. By using descriptive statistics, the authors highlighted the diagnostic issues related to the clinical presentation, radiological features, and histology of peri-implant OSCCs. Results: A total of 13 women and 8 men with a mean age of 70.6 ± 11.7 years met the inclusion criteria; the medical history of the participants showed potentially malignant disorders (OPMDs) in 52.4% of patients, whereas 14.3% had already developed an OSCC. The patients showed 24 peri-implant OSCCs; the clinical presentation was leuko-erythroplakia-like (41.7%) or erythroplakia-like (58.3%), thus simulating peri-implantitis; in addition, 52.0% of dental implants involved had a probing pocket depth ≥ 10 mm, further mimicking peri-implantitis. Panoramic radiograms and cone beam computed tomography were of little use in studying bundle bone–implant interfaces; in particular, the tomography showed circumferential bone resorption only in peri-implantitis-like OSCCs. In total, 91.6% of histological examinations of OSCCs showed peri-implantitis-like inflammation; early-stage lesions (pTNM I-II) accounted for 33.3%, whereas late-stage lesions (pTNM III-IV) accounted for 66.7%; lymph nodal metastases occurred in 25.0% and 62.5%, respectively. The mean follow-up was 3.4 ± 1.0 years; all patients with OPMDs had poorly differentiated tumors and thus showed a worse prognosis than those without OPMDs (mean disease-free survival of 15.5 ± 7.7 months and 44.7 ± 12.1 months, respectively). Conclusions: The results of the study showed that peri-implant OSCCs occurred most frequently in patients with OPMDs or previous OSCC; in addition, peri-implant OSCCs required demolition rather than conservative excision, and the prognosis of patients strictly depended on the grade of the cancer. In the authors’ experience, the clinical–radiological presentation simulating peri-implantitis was the feature that concurred most in complicating the diagnosis of those tumors. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity and is frequently diagnosed at an advanced stage, resulting in poor prognosis and limited treatment options. Identifying reliable biomarkers that can predict tumor progression and serve as therapeutic targets remains an urgent clinical need. Methods: To identify key molecular drivers in OSCC, we performed an integrative bioinformatics analysis of five OSCC-related microarray datasets from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and subjected to functional enrichment, protein–protein interaction (PPI) network construction, and hub gene ranking using Cytoscape. Candidate genes were further validated using TCGA, UALCAN, and the Human Protein Atlas. In vitro functional assays were performed to evaluate the effect of TK1 knockdown on cell migration. Results: A total of 138 common DEGs were identified across datasets. GO enrichment revealed that these genes were associated with cell proliferation, extracellular matrix organization, and metastasis-related processes. Thymidine kinase 1 (TK1) was identified as a key hub gene and found to be consistently overexpressed in OSCC tissues. Kaplan–Meier analysis showed that high TK1 expression correlated with poor overall survival in head and neck cancer. TK1 knockdown in OSCC cell lines significantly impaired cell migration and wound-healing ability. Conclusions: Our findings suggest that TK1 plays an active role in promoting OSCC progression and may serve as a prognostic biomarker and potential therapeutic target for metastatic OSCC. Full article

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of OSCC diagnosis and treatment. This review provides a comprehensive synthesis of early molecular diagnostic strategies, including biomarker discovery using next-generation sequencing, liquid biopsy, and salivary exosomal microRNAs. In addition, we highlight the emerging role of non-invasive optical imaging technologies and their clinical integration for improved surgical precision and early lesion detection. This review also discusses evolving therapeutic approaches, including immunotherapy, neoadjuvant chemotherapy, and patient-centered multimodal regimens tailored through molecular profiling. We emphasized balancing therapeutic efficacy with the quality of life in patients undergoing chemoradiotherapy. The convergence of multi-omics, artificial intelligence, and precision medicine holds promise for revolutionizing early detection and personalized treatment of OSCC, ultimately improving patient survival and clinical outcomes. Full article

Background: Circulating cell-free DNA (cfDNA) has been widely used as a prognostic marker for different cancers. Objective: In this study, we used 30 cfDNA samples from oral squamous cell carcinoma (OSCC), 199 public OSCC samples, and 192 normal samples to study various correlation factors that could improve the early-stage diagnostics and/or prognosis of OSCC. Methods: The statistical correlation between healthy and OSCC patients was done and deep sequencing analyses was performed to study various genomic alterations likes copy number variation (CNV), and single nucleotide variants (SNVs), gene fusion and genomic integration of viruses. Results: We found that the OSCC patient cfDNA concentration can serve as an indicator of tumor stage, malignancy, and survival prognosis. Deep genome sequencing of cfDNA revealed genomic alterations, such as CNVs, fusion genes, and viral integrations. The CNV analysis suggested a correlation with amplification and deletion in chromosomes at loci 1q, 2q, 3p, 3q, and chromosome 8 at loci q22. Moreover, at these loci, amplification of TP53, PIK3CA, and other genes related to keratinization in OSCC patients was observed. In addition, we identified a novel abundant fusion gene, TRMO-TRNT1 ‘chimera’, in seven high-grade tumor samples. The parental genes of this chimera, TRMO and TRNT1, are known to play roles in tRNA modification and DNA repair, respectively. We have identified SNVs in our OSCC cohort. Some of these SNVs, like KMT2C, MUC3A, and MUC6, have been identified as common cases in different cancer populations. Finally, we detected contigs integrations of human papillomavirus, simian virus, and enterovirus in the OSCC samples, which may point to the potential causes of OSCC. Conclusions: Our results indicate that the liquid biopsy technique may thus serve as a sensitive tool to study OSCC patient genomic alterations by exploring cfDNA circulating in the plasma, providing an easy-to-use blood test in the future. Full article

To determine predictive biomarkers for prognosis by analyzing the association between tumor mutational burden (TMB) and mutant genes in patients with oral squamous cell carcinoma (OSCC) and to validate PCLO as an OSCC predictive biomarker, OSCC genetic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. Immune cell infiltration analysis and visualization were performed using R software. The relationships between overall survival (OS) and mutant genes or clinicopathological factors were investigated by Kaplan–Meier analysis and Cox regression analysis, respectively. Gene set enrichment analysis (GSEA) was used to explore the associations between mutant genes and functional pathways. Immunohistochemistry was performed to verify the presence of the piccolo protein in OSCC tissues. Finally, 17 mutated genes shared between TCGA and the ICGC database were detected. The TMB in the PCLO-mutated group was found to be significantly greater than that in the PCLO wild-type group, and PCLO mutation was associated with poor OS. Cox regression analysis revealed that PCLO is a significant prognostic factor for OSCC. GSEA and immune cell infiltration analysis revealed that PCLO is associated with the immune system, which suggests that PCLO mutation might affect the immune response. PCLO expression was considerably higher in OSCC tissues with PCLO mutations than in corresponding normal epithelium tissues and OSCC tissues without PCLO mutations (p < 0.05). PCLO mutation could serve as a promising predictive biomarker for prognosis in patients with OSCC. Full article

Background/Objectives: Local and systemic factors, including nutritional status, influence the prognosis of oral squamous cell carcinoma (OSCC). Skeletal muscle mass (SMM) loss is a poor prognostic factor in older patients and those with cancer. Herein, we examined the SMM index (SMI), rates of surgical site infection (SSI), and prognosis of 92 patients (59 males and 33 females) who underwent resection and free flap reconstructive surgery (FFRS) between 2013 and 2021. Methods: Preoperative computed tomography was performed to measure SMM at L3. The median SMI was 45.94 and 38.03 cm²/m² in males and females, respectively. Patients were classified into low and high SMI groups based on median SMI, and overall survival (OS) was analyzed. Results: Overall, 47 (51.1%) and 45 (48.9%) patients had low and high SMIs, respectively. SSI occurred in 11 (12.0%) patients; wound dehiscence and delayed wound healing were observed in 22 (23.9%). SSI rates were not significantly different between the low and high SMI groups. Conversely, OS was significantly associated with age, pathological N (pN), extranodal extension (ENE), and SMI (high, 81.1%; low, 60.2%). Univariate analyses revealed significant associations between OS and age (≥65 vs. <65 years), SMI (low vs. high), pN (present vs. none), ENE (present vs. none), and albumin (<4.0 vs. ≥4.0 mg/dL). Cox multivariate analysis included SMI (low vs. high; hazard ratio [HR]: 2.339, 95% confidence interval [CI]: 1.008–5.429; p = 0.015) and ENE (present vs. none; HR: 7.727, 95% CI: 3.083–19.368; p < 0.001). Conclusions: SMI and ENE were identified as independent predictive factors of OS in patients with OSCC undergoing FFRS. Full article

Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes in OSCC have been related to grade, invasion, and metastasis. The presence of 9-O-acetylated sialic acid (Neu5,9Ac₂) in OSCC cells and its potential expression, modification, and role are unknown. This study aimed to analyze the expression of Neu5,9Ac₂ using the Macrobrachium rosenbergii lectin (MrL) that recognizes this sialic acid (Neu5Ac) residue and also compare its effect on the SCC-152 cell line (CRL-3240, ATCC) and immortalized keratinocytes (HaCaT) as a control. We observed by immunocytochemistry that SCC-152 cells expressed more Neu5,9Ac₂ compared to HaCaT cells; the specificity of MrL was confirmed after the sialidase treatment of cells in which the loss of lectin’s recognition of Neu5,9Ac₂ was observed. The electrophoretic profile was similar between both cell line types; however, the Western blot showed differences in the glycoprotein patterns recognized by lectin for each cell type. MrL increased the proliferation of SCC-152 cells, as well as the integrity and morphology of the colonies. Therefore, our results suggest that Neu5,9Ac₂ glycosylated receptors could be involved in the survival and proliferation of OSCC cells, which offers a promising avenue for developing diagnostic and prognostic tools (tumor markers) against oral squamous cell carcinoma in the future. Full article