RESUMEN

Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.

Asunto(s)

Secuenciación del Exoma , Melanoma , Mucosa Bucal , Neoplasias de la Boca , Mutación , Perros , Melanoma/genética , Melanoma/veterinaria , Melanoma/patología , Humanos , Animales , Neoplasias de la Boca/genética , Neoplasias de la Boca/veterinaria , Neoplasias de la Boca/patología , Mucosa Bucal/patología , Mucosa Bucal/metabolismo , Línea Celular Tumoral , Enfermedades de los Perros/genética

RESUMEN

OBJECTIVE: To investigate the clinicopathological, immunohistochemical and molecular features of histiocytic sarcomas affecting the oral cavity. METHODS: Pathology files of two institutions were searched for cases of histiocytic sarcoma, and new H&E-stained slides and immunohistochemistry reactions evaluated for diagnosis confirmation. Molecular screening for KRAS and PIK3CA mutations was performed through polymerase chain reaction (PCR) followed by Sanger sequencing. BRAFp.V600E mutation was assessed by pyrosequencing. Clinical data regarding sex, age, tumor location, systemic manifestations, clinical presentation, follow-up time, treatment applied and status at last follow-up were collected from patients' pathology and medical files. RESULTS: Three cases were retrieved during the period investigated (2000-2023). Two females and one male were affected, with a wide age range, involving the tongue, palate and gingiva. Histopathologically, the neoplasms presented as highly pleomorphic atypical cells distributed diffusely with infiltration of normal structures. All cases demonstrated histiocytic differentiation expressing CD68 and CD163, and a high Ki67 expression. Genetic mutations were evaluated in two cases. One case harboured BRAF-V600E mutation, but not in KRAS and PIK3CA, while the second case did not show mutation in BRAF-V600E, KRAS and PI3KCA. One patient was lost, and two patients died after eight and four months of follow-up. CONCLUSION: Histiocytic sarcomas involving the oral cavity are extremely rare, and may represent dissemination of a systemic condition. It has an aggressive biological behaviour with a poor overall prognosis.

Asunto(s)

Fosfatidilinositol 3-Quinasa Clase I , Sarcoma Histiocítico , Inmunohistoquímica , Neoplasias de la Boca , Mutación , Proteínas Proto-Oncogénicas B-raf , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Masculino , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patología , Femenino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Adulto , Biomarcadores de Tumor/genética , Anciano , Reacción en Cadena de la Polimerasa

Asunto(s)

Metástasis Linfática , Neoplasias de la Boca , Reacción en Cadena en Tiempo Real de la Polimerasa , Ganglio Linfático Centinela , Humanos , Metástasis Linfática/diagnóstico , Metástasis Linfática/genética , Metástasis Linfática/patología , Neoplasias de la Boca/patología , Neoplasias de la Boca/genética , Proyectos Piloto , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela/métodos

RESUMEN

BACKGROUND: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. METHODS: Case-control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single-nucleotides polymorphisms were tested for individuals with and without missing teeth. RESULTS: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). CONCLUSIONS: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de la Boca , Pérdida de Diente , Humanos , Neoplasias de la Boca/genética , Masculino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/epidemiología , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Pérdida de Diente/epidemiología , Anciano , Polimorfismo de Nucleótido Simple , Adulto , Predisposición Genética a la Enfermedad , Factores de Riesgo , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Interacción Gen-Ambiente

RESUMEN

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Emetina/metabolismo , Emetina/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Histonas/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Células Madre Neoplásicas/patología , Sirtuina 1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba

RESUMEN

BACKGROUND AND OBJECTIVES: In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis? MATERIAL AND METHODS: The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting. RESULTS: A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak. CONCLUSION: In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions.

Asunto(s)

Daño del ADN , Neoplasias de la Boca , Humanos , Carcinogénesis/genética , Ensayo Cometa/métodos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Reproducibilidad de los Resultados

RESUMEN

The objective of this study was to assess the remodeling-associated gene expression in the mandible of patients diagnosed with oral squamous cell carcinoma (OSCC), investigating the cortical microarchitecture, and their influence on disease-free survival (DFS) and overall survival (OS) rates. A total of twenty-four patients who underwent mandibulectomy for OSCC treatment had two bone fragments harvested from the mandible for gene expression (RANK, RANKL, OPG, and SOST), and microarchitecture analysis, including bone volume, surface, mineral density, degree of anisotropy, and fractal dimension. The prognosis of the patients was assessed. The results revealed that RANK, RANKL, and SOST were predominantly downregulated, while OPG was completely downregulated. Tumors located adjacent to the posterior region of the mandible (p = 0.02), with a bone mineral density below 1.03 g/cm3 HA (p = 0.001), and a bone volume less than 86.47% (p = 0.03) were associated with poor outcomes. In conclusion, bone-remodeling-associated genes exhibited downregulation in the cortex of the mandible in OSCC patients. Additionally, the tumor's location within the mandible, bone volume, and cortical bone mineral density were identified as factors impacting DFS.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Ligando RANK/genética , Expresión Génica , Osteoprotegerina/genética

RESUMEN

This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/genética , Estudios Retrospectivos , Neoplasias de la Boca/genética , Mapeo Cromosómico , Carcinoma de Células Escamosas de Cabeza y Cuello

RESUMEN

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein-Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.

Asunto(s)

Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/patología , Fosfatidilinositol 3-Quinasas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de Cabeza y Cuello/complicaciones , Mutación

RESUMEN

BACKGROUND: In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. METHODS: Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. RESULTS: Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. CONCLUSION: This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Perfilación de la Expresión Génica , Tolerancia a Radiación/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Línea Celular Tumoral , Biomarcadores , Neoplasias de Cabeza y Cuello/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Proteínas de la Membrana/genética , Fosfatidilinositol 3-Quinasas/genética

RESUMEN

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Lesiones Precancerosas , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Secuenciación del Exoma , Neoplasias de Cabeza y Cuello/patología , Mucosa Bucal/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología

RESUMEN

In the last decades, the search for biomarkers for response to therapy and prognosis, with potential of providing information about the likely course and outcome of disease, has been intense in oral squamous cell carcinomas. Although several biomarkers, ranging from genetic and molecular alterations to clinical and histopathological features, have been described, only a few of them are used in routine practice. The aim of this review is to outline the recent advances in oral squamous cell carcinomas biomarkers, exploring those related to clinical and histopathological features, cancer cells and components of the tumor microenvironment. Future directions, highlighting the main issues that limit the clinical application of many of the potential biomarkers, are discussed.

Asunto(s)

Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Biomarcadores de Tumor/genética , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Microambiente Tumoral

RESUMEN

Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30-1.18), GSTT1 (OR: 1.18; 95%CI:0.49-2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18-3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47-1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Nicotiana/genética , Carcinoma de Células Escamosas/genética , Genotipo , Polimorfismo Genético , Carcinoma de Células Escamosas de Cabeza y Cuello , Predisposición Genética a la Enfermedad , No Fumadores , Neoplasias de la Boca/genética , ADN

RESUMEN

INTRODUCTION: Leukoplakia is one of the most frequently found lesions in the oral cavity, with a probability of 17 to 24% of becoming malignant cells in a period of 30 years. OBJECTIVE: To identify differentially expressed gene profiles of leukoplakia and its progression to oral squamous cell carcinoma, essential for the discovery of new biomarkers to predict and prevent the presence of diseases in the oral cavity. METHODS: Initially, gene profiles of GSE85514 and GSE160042 from the Gene Expression Omnibus database were used. Differentially expressed genes were identified using GEO2R. The CLUEGO plugin in Cytoscape was used for DEG functionality and enrichment analysis. Finally, a protein-protein interaction (PPI) network was constructed using Cytoscape from data collected online from the STRING server. RESULTS: According to the MCC algorithm, the 10 most found gene sequences were HNRNPU, SMC1A, PAFAH1B1, EHMT1, SPTBN4, OLFM1, NCAM1, SF3B3, FGF2, and UBE2I; with HNRNPU, SMC1A, and PAFAH1B1 being the most representative of the modules. CONCLUSIONS: We were able to describe the gene sequences that promote the progression from leukoplakia to oral squamous cell carcinoma. Within these genes, the HNRNPU, SMC1A, and PAFAH1B1 constitute the main promising therapeutic targets to counteract the progression of oral cancer, they could also be important biomarkers for the diagnosis and classification of the disease.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Carcinoma de Células Escamosas/genética , Biología Computacional , Leucoplasia , Expresión Génica

RESUMEN

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.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Liquen Plano Oral , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/genética , Liquen Plano Oral/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Oncogenes , Carcinogénesis/genética

RESUMEN

Oral cancer is a disease with high incidence and mortality worldwide, and its treatment still needs to be improved. The search for new therapies using natural products is strongly supported, given the wide chemical range of these compounds. In addition, phytochemicals can exert antitumor activities by several mechanisms of action, including the modulation of non-coding RNAs. Thus, in this review, we discussed the role of non-coding RNAs, including circular RNAs, microRNAs, and long non-coding RNAs, in oral cancer and presented their potential as treatment targets using natural products. Some natural products capable of being used to treat oral cancer have been suggested.

Asunto(s)

Productos Biológicos , MicroARNs , Neoplasias de la Boca , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Circular , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , MicroARNs/genética , Productos Biológicos/uso terapéutico

RESUMEN

BACKGROUND: Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT). MATERIALS AND METHODS: Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression of CYP1A1, GSTM1, GSTP1, and GSTT1 genes by the RT-qPCR method. RESULTS: There were significant differences in the AUDIT score and CYP1A1 expression between cancer and control groups. Participants in advanced stages, whether due to tumor size or regional metastasis, showed significant differences in the duration of tobacco use, FTCD, AUDIT score, and CYP1A1 expression when compared to patients in early stages. Among subjects without cancer, we found a significant correlation between participant age and GSTP1 expression. Furthermore, the expression of GSTP1 was significantly correlated with the number of cigarettes smoked per day, duration of tobacco use, and FTCD. CONCLUSIONS: Questionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies.

Asunto(s)

Alcoholismo , Neoplasias de la Boca , Consumo de Bebidas Alcohólicas , Estudios de Casos y Controles , Citocromo P-450 CYP1A1/genética , Detección Precoz del Cáncer , Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Humanos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Polimorfismo Genético , Nicotiana

RESUMEN

Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Anciano , Carcinoma de Células Escamosas/genética , Daño del ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , No Fumadores , Fumadores

RESUMEN

OBJECTIVES: This study aimed to investigate the detection of Epstein-Barr virus (EBV) in oral squamous cell carcinoma (OSCC) and to verify the concordance of EBV-DNA frequency in subgingival sites and in the OSCC. METHODS: A cross-sectional study with 30 OSCC patients, aged from 44 to 88 years old, was conducted. Samples were collected in subgingival sites and at the OSCC, then submitted to DNA isolation, qPCR, and genotyping. Descriptive statistic was performed to report the frequency of EBV-DNA in all samples, and McNemar test was applied to verify the concordance among the EBV-DNA frequency in both sites. RESULTS: The individuals presented 62 years old in average, and the majority were male (66.6%). EBV-DNA was detected in 56.7% OSCC lesions. Among the subgroup of 19 dentate individuals, high concordance (73.7%) in both EBV-DNA detection and the absence in subgingival sites and OSCC was observed, and it was statistically significant (p < 0.05). CONCLUSIONS: We report the notable occurrence of EBV-DNA in OSCC; also, the presence of EBV in periodontal sites may contribute to find it in OSCC, although the possible contribution of EBV in the OSCC remains to be investigated. CLINICAL RELEVANCE: The identification of this easily accessible site of EBV latent infection may help to improve the patient's quality of life by maintenance of oral/periodontal health condition and preventing further possible disorders related to the virus, and also encourages new approaches for investigating EBV, periodontitis, and OSCC.

Asunto(s)

Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Estudios Transversales , Femenino , Herpesvirus Humano 4/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Bolsa Periodontal , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello

RESUMEN

A pesar de que los procesos epigenéticos son estudiados ampliamente de forma general, no se habían relacionado, hasta ahora, a las alteraciones genéticas más tradicionales asociadas en la etiopatogenia del cáncer oral. La visión de carcinogénesis tradicional y la de la epigenética convergen en las mismas vías moleculares involucradas en el desarrollo del cáncer, potenciándose durante el proceso de carcinogénesis oral. A continuación se realizará una revisón de las siguientes vías moleculares VEGF-C /VEGFR; HB-EGF /EGFR; Wnt /B-catenina y las ciclinas, desde un punto de vista genético y epigenético para establecer su conexión durante el proceso de carcinogénesis oral.

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Although epigenetic processes are widely studied, no one has related them to the classical genetic processes in oral cancer etiopathogenesis. The traditional carcinogenesis and epigenetic views converge in the same molecular pathways involved in cancer development, enhancing this process. This review will approach the VEGF-C/VEGFR, HB-EGF/EGFR, Wnt /B-catenin, and cyclins molecular pathways from the genetic and epigenetic views to establish their connection during the oral cancer process.

Asunto(s)

Humanos , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Epigénesis Genética/genética , Carcinogénesis/genética , Pronóstico , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/terapia , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología