RESUMO
BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a differential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Incisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.
Assuntos
Ameloblastoma , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ameloblastoma/genética , Ameloblastoma/epidemiologia , Estudos Transversais , América Latina , Paracoccidioidomicose/epidemiologia , Estudos Retrospectivos , Neoplasias da Língua/patologia , Neoplasias da Língua/genéticaRESUMO
BACKGROUND: Stemness factors associated with tumorigenesis in different types of cancers have not been specifically studied in oral tongue SCC (OTSSC). Here, we aimed to quantify expression levels and distribution of KLF4 and SOX2, two relevant stemness factors, in oral SCC including OTSCC samples from different subsites. METHODS AND RESULTS: We determined KLF4 and SOX2 expression levels by immunostaining 35 biopsies of OSCC. Stained wholeslide images were digitized and subjected to automatic cell detection and unbiased quantification using Qupath software. We found statistically significant reduction in KLF4 positive cells density (p= 0.024), and fraction (p= 0.022) in OTSCC from tongue borders compared with other tongue subsites. Instead, quantitative SOX2 analysis did not show differences in expression levels between OTSCC from the borders versus OTSCC developed in others subsites. Notably SOX2 expression was revealed increased in moderately and poorly differentiated OSCC compared with well differentiated ones (positive cells density p= 0.025, fraction p= 0.006). No significant correlation between KLF4 and SOX2 expression was observed, neither in OSCC nor in OTSCC. CONCLUSIONS: KLF4 and SOX2 exhibit opposite expression profiles regarding subsite localization and differentiation level in OSCC. Our study prompts future OTSCC prospective studies looking for clinical prognosis to incorporate detailed subsite information in the analysis.
Assuntos
Neoplasias Bucais/metabolismo , Fatores de Transcrição SOXB1/biossíntese , Fatores de Transcrição SOXB1/metabolismo , Neoplasias da Língua/metabolismo , Estudos de Avaliação como Assunto , Humanos , Fator 4 Semelhante a Kruppel/biossíntese , Fator 4 Semelhante a Kruppel/genética , Fator 4 Semelhante a Kruppel/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Gradação de Tumores , Prognóstico , Fatores de Transcrição SOXB1/genética , Neoplasias da Língua/genética , Neoplasias da Língua/patologiaRESUMO
The aim of this study was to explore the effect of hsa_circ_0002162 on regulating cell proliferation, apoptosis, and invasion, and investigate its potential target microRNA (miRNA) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0002162 expression was detected in human TSCC cell lines and human oral keratinocytes (HOK) cell line. Cell proliferation, apoptosis, invasion, and candidate target miRNA expressions were detected in hsa_circ_0002162 knockdown-treated CAL-27 cells and hsa_circ_0002162 overexpression-treated SCC-9 cells. In the rescue experiment, miR-33a-5p knockdown plasmid was transfected into hsa_circ_0002162 knockdown-treated CAL-27 cells, while miR-33a-5p overexpression plasmid was transfected into hsa_circ_0002162 overexpression-treated SCC-9 cells. Subsequently, cell proliferation, apoptosis, and invasion were detected, and then luciferase reporter assay was performed. Hsa_circ_0002162 expression was increased in human TSCC cell lines SCC-9, CAL-27, HSC-4, and SCC-25 compared with HOK. In CAL-27 cells, hsa_circ_0002162 knockdown inhibited cell proliferation and invasion and promoted apoptosis. In SCC-9 cells, hsa_circ_0002162 overexpression enhanced cell proliferation and invasion and suppressed apoptosis. Furthermore, a negative regulation of hsa_circ_0002162 on miR-33a-5p (but not miR-302b-5p and miR-545-5p) was observed. In the rescue experiment, miR-33a-5p knockdown increased cell proliferation and invasion, and decreased apoptosis in hsa_circ_0002162 knockdown-treated CAL-27 cells, whereas miR-33a-5p overexpression decreased cell proliferation and invasion, but increased apoptosis in hsa_circ_0002162 overexpression-treated SCC-9 cells. The luciferase reporter assay showed the direct binding of hsa_circ_0002162 to miR-33a-5p. In conclusion, hsa_circ_0002162 had an important role in malignant progression of TSCC through targeting miR-33a-5p.
Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias da Língua , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , RNA Circular , Língua , Neoplasias da Língua/genéticaRESUMO
Abstract Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.
Assuntos
Humanos , Neoplasias da Língua/genética , Carcinoma de Células Escamosas/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , GenótipoRESUMO
The aim of this study was to explore the effect of hsa_circ_0002162 on regulating cell proliferation, apoptosis, and invasion, and investigate its potential target microRNA (miRNA) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0002162 expression was detected in human TSCC cell lines and human oral keratinocytes (HOK) cell line. Cell proliferation, apoptosis, invasion, and candidate target miRNA expressions were detected in hsa_circ_0002162 knockdown-treated CAL-27 cells and hsa_circ_0002162 overexpression-treated SCC-9 cells. In the rescue experiment, miR-33a-5p knockdown plasmid was transfected into hsa_circ_0002162 knockdown-treated CAL-27 cells, while miR-33a-5p overexpression plasmid was transfected into hsa_circ_0002162 overexpression-treated SCC-9 cells. Subsequently, cell proliferation, apoptosis, and invasion were detected, and then luciferase reporter assay was performed. Hsa_circ_0002162 expression was increased in human TSCC cell lines SCC-9, CAL-27, HSC-4, and SCC-25 compared with HOK. In CAL-27 cells, hsa_circ_0002162 knockdown inhibited cell proliferation and invasion and promoted apoptosis. In SCC-9 cells, hsa_circ_0002162 overexpression enhanced cell proliferation and invasion and suppressed apoptosis. Furthermore, a negative regulation of hsa_circ_0002162 on miR-33a-5p (but not miR-302b-5p and miR-545-5p) was observed. In the rescue experiment, miR-33a-5p knockdown increased cell proliferation and invasion, and decreased apoptosis in hsa_circ_0002162 knockdown-treated CAL-27 cells, whereas miR-33a-5p overexpression decreased cell proliferation and invasion, but increased apoptosis in hsa_circ_0002162 overexpression-treated SCC-9 cells. The luciferase reporter assay showed the direct binding of hsa_circ_0002162 to miR-33a-5p. In conclusion, hsa_circ_0002162 had an important role in malignant progression of TSCC through targeting miR-33a-5p.
Assuntos
Humanos , Neoplasias da Língua/genética , Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Língua , Linhagem Celular Tumoral , RNA CircularRESUMO
Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.
Assuntos
Carcinoma de Células Escamosas , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias da Língua , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Neoplasias da Língua/genéticaRESUMO
Metastasis of head and neck tumors is responsible for a high mortality rate. Understanding its biochemistry may allow insights into tumorigenesis. To that end we carried out RNA-Seq analyses of 5 SCC9 derived oral cancer cell lines displaying increased invasive potential. Differentially expressed genes (DEGs) were annotated based on p-values and false discovery rate (q-values). All 292 KEGG pathways related to the human genome were compared in order to pinpoint the absolute and relative contributions to the invasive process considering the 8 hallmarks of cancer plus 2 new defined categories, as well as we made with our transcriptomic data. In terms of absolute contribution, the highest correlations were associated to the categories of evading immune destruction and energy metabolism and for relative contributions, angiogenesis and evading immune destruction. DEGs were distributed into each one of all possible modes of regulation, regarding up, down and continuum expression, along the 3 stages of metastatic progression. For p-values twenty-six genes were consistently present along the tumoral progression and 4 for q-values. Among the DEGs, we found 2 novel potentially informative metastatic markers: PIGG and SLC8B1. Furthermore, interactome analysis showed that MYH14, ANGPTL4, PPARD and ENPP1 are amenable to pharmacological interventions.
Assuntos
Regulação Neoplásica da Expressão Gênica , Evasão da Resposta Imune , Neovascularização Patológica/genética , Neoplasias da Língua/genética , Transcriptoma , Linhagem Celular Tumoral , Humanos , Metástase Neoplásica , Neoplasias da Língua/imunologia , Neoplasias da Língua/patologiaRESUMO
BACKGROUND: DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histologic, and survival parameters in oral tongue squamous cell carcinoma, to investigate a possible role for those proteins in tumor behavior. METHODS: The expression of APE-1 and XRCC-1 was evaluated by immunohistochemistry in 82 cases of oral tongue squamous cell carcinoma. Histopathological grading was performed for each case. Pearson's chi-square and Fisher's exact tests were used to determine the association between protein expressions and clinicopathological features of tumors, whereas Kaplan-Meier curves and Cox regression were used to analyze disease-specific and disease-free survival. Statistical significance was set at P ≤ 0.05. RESULTS: APE-1 was highly expressed in the nucleus and cytoplasm in 64.6% of cases, and XRCC-1 showed overexpression only in the nucleus in 61% of cases. High expression of XRCC-1 was significantly associated with tumors at early clinical stages (I and II, P < 0.01) and nodal status (P = 0.03). Both proteins were not associated with other clinical parameters, histopathological grading, or survival. CONCLUSIONS: DNA base excision repair proteins APE-1 and XRCC-1 are upregulated in oral tongue squamous cell carcinoma, and XRCC-1 expression is associated with better clinical staging and nodal status.
Assuntos
Carcinoma de Células Escamosas/genética , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Neoplasias da Língua/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Núcleo Celular/genética , Criança , Citoplasma/genética , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Regulação para Cima , Adulto JovemRESUMO
AIMS: Metallothioneins (MTs) are proteins associated with the carcinogenesis and prognosis of various tumours. Previous studies have shown their potential as biomarkers in oral squamous cell carcinoma (OSCC). Aiming to understand more clearly the function of MTs in OSCC we evaluated, for the first time, the gene expression profile of MTs in this neoplasm. MATERIALS AND RESULTS: Tissue samples from 35 cases of tongue and/or floor of mouth OSCC, paired with their corresponding non-neoplastic oral mucosa (NNOM), were retrieved (2007-09). All tissues were analysed for the following genes using TaqMan(®) reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays: MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT3 and MT4. The expression of MT1B and MT1H was seldom detected in both OSCC and NNOM. A significant loss of MT1A, MT1X, MT3 and MT4 expression and gain of MT1F expression was observed in OSCC, compared to NNOM. Cases with MT1G down-regulation exhibited the worst prognoses. The up-regulation of MT1X was restricted to non-metastatic cases, whereas up-regulation of MT3 was related to cases with lymph node metastasis. CONCLUSIONS: Metallothionein mRNA expression is altered significantly in oral squamous cell carcinomas. The expression of MT1G, MT1X and MT3 may aid in the prognostic discrimination of OSCC cases.
Assuntos
Carcinoma de Células Escamosas/genética , Metalotioneína/genética , Neoplasias Bucais/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Regulação para Baixo , Feminino , Humanos , Masculino , Metaloproteinase 16 da Matriz/genética , Pessoa de Meia-Idade , Mucosa Bucal/enzimologia , Neoplasias Bucais/patologia , Prognóstico , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias da Língua/genética , Neoplasias da Língua/patologia , Regulação para CimaRESUMO
Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.