Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
1.
Crit Rev Oncol Hematol ; 179: 103792, 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35973662

RESUMO

Adenoid cystic carcinoma (ACC) is a biphasic malignant lesion that can develop at various anatomical sites. Salivary and lacrimal ACC lesions have a high risk of local invasion, metastasis, and poor prognosis. In more distant organs, such as the breast, ACC is a rarer and less aggressive lesion. One of the major predictors of mortality of ACC is perineural invasion, which can be seen in 30 % of breast lesions, 85% of salivary lesions, and almost 100 % of lacrimal gland tumors. The biological differences between these three ACC tumors are still poorly understood. We focused on the current understanding of the genetic variations observed on ACC tumors and prognostic differences associated with distinct anatomical sites. A special effort was made to present the currently available therapies alongside the emerging strategies under development.

4.
J Appl Oral Sci ; 30: e20210702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584505

RESUMO

BACKGROUND: Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. OBJECTIVE: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. METHODOLOGY: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). RESULTS: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). CONCLUSION: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.


Assuntos
Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Tonsilares , Carcinoma de Células Escamosas/patologia , Humanos , Imuno-Histoquímica , Prognóstico , Neoplasias Tonsilares/patologia
5.
Oral Oncol ; 127: 105777, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35189584

RESUMO

Salivary gland carcinomas (SGC) are rare tumors of heterogeneous morphology and many histological subtypes. Like other tumors, the SGC mass consists of a varied population of malignant cells and a diverse array of immune cells, cancer-associated fibroblasts, cytokines, chemokines, extracellular matrix proteins, and metalloproteinases, collectively known as the tumor microenvironment (TME). This chaotic network serves as an important physical mediator of cancer cell growth. In this review, we provided current insights into the TME of some of the most common SGC. Here, we highlighted the histological heterogeneity of these tumors, delineated the nature/intensity of inflammatory infiltrates, and the mechanisms involved in immunological escaping related to each SGC subtype.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma , Neoplasias das Glândulas Salivares , Fibroblastos Associados a Câncer/metabolismo , Humanos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Microambiente Tumoral
6.
Arch Oral Biol ; 136: 105373, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35180549

RESUMO

OBJECTIVE: To integrate all the available data published in the English literature regarding the protein diagnostic and/or prognostic markers in salivary gland tumors identified by mass spectrometry (MS)-based discovery proteomics. DESIGN: An extensive search was carried out using MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases. Manual searching in Google Scholar and assessment of the reference list of the included articles also was performed. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal tool for the specific type of study. RESULTS: A total of 1092 articles were initially retrieved within which 6 were used for data extraction, resulting in 145 cases of salivary gland tumors. The data was composted by eleven salivary gland tumor types. In total, 2136 proteins were detected by MS-based discovery proteomics in salivary gland tumors. Ninety-one proteins were proposed as potential diagnostic and/or prognostic markers. Of these, some have been identified in one or more studies, whereas fifteen were in common across studies and a total of seventy-six were non-repeat proteins. CONCLUSION: In summary, we compiled data about the proteomic profile of potential diagnostic and/or prognostic protein markers of the salivary gland tumors detected by MS-based discovery proteomics. The proteins ANXA1, ANXA5, CAPG, CRYAB, FGB, GNB2L1, IGHG1, PPIA, S100A9, and SOD1 were proposed as the most common potential diagnostic markers of salivary gland tumors.


Assuntos
Proteômica , Neoplasias das Glândulas Salivares , Anexina A5 , Biomarcadores , Humanos , Espectrometria de Massas , Neoplasias das Glândulas Salivares/diagnóstico
7.
Oral Oncol ; 126: 105779, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35183913

RESUMO

INTRODUCTION: Sinonasal undifferentiated carcinoma (SNUC) is a rare tumor highly aggressive most frequently arise in the maxillary sinus and nasal cavity. Oral involvement is extremely rare. CASE REPORT: A 62-years-old male presents a large infiltrative mass involving the hard palate and left alveolar ridge. Computed tomography showed bone destruction and invasion of paranasal sinuses and orbits. Histology revealed a malignant neoplasm consisting of small round cells with minimal cytoplasm and hyperchromatic nuclei without any connection with the oral mucosal epithelium. Immunohistochemical analysis showed epithelial origin (CK-7+, CK-20+, AE1/AE3+, EMA+) and lacked strong evidence of squamous and neuroendocrine differentiation (p63-, 34ßE12-, NSE-/+, chromogranin-, synaptophysin-). TTF-1 negative ruled out the metastatic origin. A diagnosis of SNUC subtype positive for SMARCB1 (INI1) was reached. The patient was submitted to concurrent radiotherapy and chemotherapy without signs of recurrence after 2 years. CONCLUSION: SNUC involving the oral cavity is a rare malignancy that may mimic symptoms of dental infection or sinusitis. A careful correlation of clinical, microscopic, and immunohistochemical characteristics is mandatory for early diagnosis.


Assuntos
Carcinoma , Neoplasias do Seio Maxilar , Neoplasias dos Seios Paranasais , Biomarcadores Tumorais/análise , Carcinoma/diagnóstico , Carcinoma/patologia , Humanos , Masculino , Neoplasias do Seio Maxilar/diagnóstico , Neoplasias do Seio Maxilar/patologia , Pessoa de Meia-Idade , Cavidade Nasal/patologia , Neoplasias dos Seios Paranasais/patologia
8.
Oral Oncol ; 125: 105680, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35026669

RESUMO

INTRODUCTION: Spindle cell carcinoma (SpCC) or sarcomatoid carcinoma, is a rare variant of squamous cell carcinoma (SCC) that has a variable proportion of carcinomatous and sarcomatous components. Here, we reported an immunohistochemical study of a spindle cell carcinoma with a challenging morphological diagnosis. CASE REPORT: A 50-year-old woman with a previous history of nodular melanoma was referred for evaluation of a painful papule in the lower lip. After surgical resection, neoplastic cells showed focal positivity for CK-14, αSMA, p63, and confirmed the strong positivity for S100 and vimentin. Tumor cells were negative for HMB-45, Melan A, SOX-10, AE1/AE3, 34ßE12, CK5-6, CAM5.2, EMA, desmin, calponin, CD10, CD34, and CD68. With these findings, a diagnosis of SpCC was rendered. The patient presented lung and dorsal metastases after 12 months and after 3 years of follow-up, the patient died. CONCLUSION: In summary, a careful correlation of microscopy and immunohistochemical characteristics is required for the proper diagnosis of this lesion.


Assuntos
Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Lábio/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia
9.
Crit Rev Oncol Hematol ; 171: 103605, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35077805

RESUMO

Salivary gland carcinomas (SGC) are aggressive cancers that arise in minor and major salivary glands. Given the complexity and the multiple subtypes of this class of tumors, diagnosis and, treatment may be challenging for clinicians. Recently the tumor microenvironment, composed mainly of immune and stromal cells are been a target for treatment. Accumulating evidence indicates that cancer immunotherapies have made a significant impact on oncologic patients, however immunotherapeutic attempts in SGC have been shown limited improvement. Advances in the models that best translate aggressive SGC are needed for the development of clinical protocols grouping immunotherapies and other classes of drugs that will promote better responses in patients with advanced SGC stages. In this review, we introduced different experimental models for SGC with a focus on tumor microenvironment highlighting potential therapy applications for each model.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Imunoterapia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Glândulas Salivares/patologia , Microambiente Tumoral
10.
Int Ophthalmol ; 42(4): 1101-1109, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34757565

RESUMO

PURPOSE: To evaluate metabolic alterations along with the carcinoma ex pleomorphic adneoma (CXPA) development of lacrimal glands (LG). METHODS: Four samples of the normal LG (NLG), 9 of pleomorphic adenoma (PA), 4 of residual PA (rPA), and 4 of CXPA of LG were included. GLUT-1, HIF-1α, FASN, and adipophilin by immunohistochemical stains were performed in the selected cases. RESULTS: Was observed higher expression of markers associated with glycolytic and lipid metabolism in the tumor tissue samples when compared to the NLG samples. Additionally, GLUT-1, FASN, and Adipophilin were more expressed in CXPA samples while HIF-1α in PA samples. CONCLUSIONS: In conclusion, our results demonstrate overexpression of FASN and Adipophilin in CXPA which may reflect a metabolic shift toward lipogenesis in cancer cells.


Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Carcinoma , Aparelho Lacrimal , Adenocarcinoma/metabolismo , Carcinoma/patologia , Humanos , Aparelho Lacrimal/patologia , Perilipina-2
11.
J. appl. oral sci ; 30: e20210702, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1375715

RESUMO

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

12.
Oral Dis ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34902207

RESUMO

OBJECTIVE: To analyze the proteomic profile of salivary pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) samples and correlate them with the malignant transformation of the PA. MATERIALS AND METHODS: Thirty samples (10 PA, 16 CXPA, and 4 residual PA) were microdissected and submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomic data and protein identification were analyzed through LC-MS/MS spectra using the MaxQuant software. RESULTS: The proteomic analysis identified and quantified a total of 240 proteins in which 135 were found in PA, residual PA, and CXPA. The shared proteins were divided into six subgroups, and the proteins that showed statistically significant differences (p > 0.05) and fold-change > or <2.5 in one subgroup to another subgroup were included. Seven proteins (Apolipoprotein A-I-APOA1, haptoglobin-HP, protein of the synaptonemal complex 1-SYCP1, anion transport protein of band 3-SLC4A1, subunit µ1 of AP-1 complex-AP1M1, beta subunit of hemoglobin-HBB, and dermcidin-DCD) were classified as potential protein signatures, being HP, AP1M1, and HBB with higher abundance for PA to residual PA, APOA1 with higher abundance for PA to CXPA, SLC4A1 with lower abundance in the PA to CXPA, SYCP1with lower abundance for residual PA to CXPA, and DCD with higher abundance in the CXPA with epithelial differentiation to myoepithelial differentiation. CONCLUSIONS: In this work, we demonstrated the comparative proteomic profiling of PA, residual PA, and CXPA, and seven were proposed as protein signatures, some of which may be associated with the malignant phenotype acquisition.

13.
Braz Oral Res ; 35: e075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495136

RESUMO

Smoking has been shown to alter innate and adaptive immune responses and is directly associated with the onset of oral squamous cell carcinoma (OSCC). The purpose of this study was to evaluate the effect of cigarette smoke exposure on dendritic cells (DCs) from OSCC patients. CD1a and CD83 antibodies were used to identify immature and mature DCs, respectively, by immunohistochemistry in OSCC samples of 24 smokers and 24 non-smokers. Density of DCs was calculated in intra and peritumoral areas. Clinical and microscopic findings were reviewed and analyzed for all patients. Smokers with OSCC had a lower density of intra and peritumoral DCs when compared to non-smokers. Tumors classified as moderately/poorly differentiated had lower peritumoral CD1a+ DCs than well-differentiated tumors (p < 0.001). Smoking contributed to a depletion of immature and mature DCs in the OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Células Dendríticas , Humanos , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
Head Neck Pathol ; 15(4): 1119-1126, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33843033

RESUMO

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki-67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Ácido Graxo Sintases/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo
15.
Oral Oncol ; 120: 105262, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33773910

RESUMO

Male patient 60-year-old was referred from another service for expert review of a lesion in the submental region. Pathological review revealed morphological features compatible with salivary gland Secretory carcinoma (SC) in cervical lymph node. The patient underwent removal of the left submandibular gland, left neck dissection and biopsy of left labial commissure region. Anatomopathological examination was observed tumor cells arranged in a solid and ductal/cystic pattern, with abundant droplets of secreted eosinophilic material within these structures and extensive hyalinized area, which presented few cells arranged in a ductal pattern. It was possible to observe the presence of extracapsular extension of neoplastic cells > 6 mm, base on this aspects, Carcinoma ex pleomorphic adenoma was suspected. Immunohistochemical panel showed positivity for mammaglobin, s100, CK7, and adipophilin and negativity for myoepithelial markers and PAS in SC cells. The myoepithelial markers showed positivity for residual cellsin hyalinized area, corresponding to residual Pleomorphic adenoma (PA). In view of these findings, the diagnosis of Secretory carcinoma ex pleomorphic adenoma (SCXPA) was established.


Assuntos
Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Biópsia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Glândula Submandibular
16.
Oral Maxillofac Surg ; 25(4): 445-456, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33666770

RESUMO

PURPOSE: Different levels of miRNA expression have been described in salivary gland tumors as a potential diagnostic marker and predictor of survival. We systematically reviewed the literature to assess the diagnostic and prognostic value of miRNAs on salivary gland tumors. METHODS: An electronic search was conducted in PubMed, Scopus, Embase, Cochrane, and Web of Science databases. In the meta-analysis, we assumed random-effects model with adjusted hazard ratio (HR) and 95% confidence intervals (95% CI). For prognostic studies, the risk of bias was assessed by Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) and Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for diagnostic studies. RESULTS: Gathered data from 1.131 patients in seven studies demonstrated that different levels of miRNA expression presented diagnostic and prognostic in SGTs. The meta-analysis showed that altered miRNA expression were associated with shortened survival (HR, 2.35, 95% CI, 1.77-3.10, P < .00001). For diagnostic meta-analysis, the overall pooled results for specificity and sensibility were 0.87-0.97 (95% CI, 0.72-1) and 0.68-0.91 (95% CI, 0.51-0.96), respectively. CONCLUSION: MicroRNAs may be useful in prognostication of patients with SGTs; however, the diagnostic value of miRNAs in SGTs is still limited.


Assuntos
MicroRNAs , Neoplasias das Glândulas Salivares , Biomarcadores Tumorais/genética , Humanos , MicroRNAs/genética , Prognóstico , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética
17.
J Matern Fetal Neonatal Med ; : 1-6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406952

RESUMO

INTRODUCTION: Placental villitis is characterized by the presence of inflammatory infiltrate in the placental villous. The objective of this study was to characterize in villitis of unknown etiology (VUE) of the human placentas the subpopulation of M1, important effector cells, and M2 macrophages, immunoregulatory cells. METHODS: Sixteen cases of VUE and three control placentas were examined using immunohistochemistry with antibodies for CD3, CD68, CD11c, and CD163. RESULTS: CD11c appeared predominantly in the inflamed villi when compared to the normal areas (p<.001). These cells corresponded to 41.2% of the macrophage population in the inflamed area and were mainly present inside the villi (36%). With regards to CD163, these cells tended to be in higher amounts in the inflamed villi when compared to CD11c and normal areas. DISCUSSION: We conclude that the almost exclusive presence of M1 macrophages in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The greater amount of M2 in villitis and normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

18.
Crit Rev Oncol Hematol ; 157: 103195, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307199

RESUMO

The myoepithelial cell seems to play an important role as a tumor suppressor in the development of carcinoma ex pleomorphic adenoma. Nevertheless, interesting aspects concerning the other side of the coin, i.e., the contribution of the myoepithelial cell to cell proliferation, were brought to light. Here we highlighted the studies in which myoepithelial cells were presented as tumor suppressors and promoters in the context of PA malignant transformation. In conclusion, even if in a paracrine way, divergent signals can alter the suppressor role of the myoepithelial cell and induce it to compose a microenvironment propitious to the tumor progression of the malignant cells. This would cause myoepithelial cells to succumb and malignant epithelial cells to initiate progression beyond the basal membrane.


Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Proliferação de Células , Transformação Celular Neoplásica , Células Epiteliais , Humanos , Microambiente Tumoral
19.
Braz. oral res. (Online) ; 35: e075, 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1339458

RESUMO

Abstract Smoking has been shown to alter innate and adaptive immune responses and is directly associated with the onset of oral squamous cell carcinoma (OSCC). The purpose of this study was to evaluate the effect of cigarette smoke exposure on dendritic cells (DCs) from OSCC patients. CD1a and CD83 antibodies were used to identify immature and mature DCs, respectively, by immunohistochemistry in OSCC samples of 24 smokers and 24 non-smokers. Density of DCs was calculated in intra and peritumoral areas. Clinical and microscopic findings were reviewed and analyzed for all patients. Smokers with OSCC had a lower density of intra and peritumoral DCs when compared to non-smokers. Tumors classified as moderately/poorly differentiated had lower peritumoral CD1a+ DCs than well-differentiated tumors (p < 0.001). Smoking contributed to a depletion of immature and mature DCs in the OSCC.

20.
Sci Rep ; 10(1): 17039, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046743

RESUMO

We conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3'-untranslated region (3'-UTR) of carcinogenesis-related genes, and one SNV was selected for data validation in stage 2 by TaqMan assays in 250 OPSCC patients and 250 controls. The ERP29 c.*293A > G (rs7114) SNV located at miR-4421 binding site was selected for data validation among 46 SNVs. The ERp29 and miR-4421 levels were evaluated by quantitative-PCR and Western blotting. Interaction between miR-4421 with 3'-UTR of ERP29 was evaluated by luciferase reporter assay. Event-free survival (EFS) was calculated by Kaplan-Meier and Cox methods. ERP29 GG variant genotype was more common in OPSCC patients than in controls (6.4% vs 3.6%, p = 0.02; odds ratio: 5.67; 95% confidence interval (CI) 1.27-25.26). Shorter EFS were seen in the base of tongue (BT) SCC patients with GG genotype (0.0% vs 36.2%, p = 0.01; hazard ratio: 2.31; 95% CI: 1.03-5.15). Individuals with ERP29 AG or GG genotypes featured lower levels of ERP29 mRNA (p = 0.005), ERp29 protein (p < 0.001) and higher levels of miR-4421 (p = 0.02). The miR-4421 showed more efficient binding with 3'-UTR of the variant G allele when compared with wild-type allele A (p = 0.001). Our data suggest that ERP29 rs7114 SNV may alter the risk and prognosis of OPSCC due to variation in the ERp29 production possibly modulated by miR-4421.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Proteínas de Choque Térmico/genética , MicroRNAs/genética , Neoplasias Orofaríngeas/genética , Adulto , Alelos , Sítios de Ligação , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...