48 resultados para microarray profiling


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Patologia - FMB

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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(Microarray technology in study of head neck cancer). The microarray technology is a tool for global analysis of gene expression that allows investigating hundreds or thousands of genes in a sample using a hybridization reaction. This technology is based on hybridization between labeled targets derived from biological samples and an array of many DNA probes immobilized on a solid matrix, representing the genes of interest. The simultaneous study of hundreds of genes became the microarray technique a very important tool of global analysis, with applications in several areas, including the study of the development of cancer. Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide, with a global annual incidence of 780,000 new cases. Large-scale studies involving microarrays have identified specific gene expression signatures associated with expression changes in HNSCC samples compared to normal tissue, as well as genes involved in clinical outcome and metastasis. However, the considerable heterogeneity among these studies occurs due to experimental design, number of samples, disease sites and stage, choice of microarray platform and results validation. Thus, there is much to be validated, before the technique has clinical utility. In relation to head and neck neoplasia, the large-scale gene analysis is very important, since the clinical and histopathological methods currently used appear to be insufficient to predict clinical progression and response to treatment. Thus, this approach could result in more effective diagnostic and prognostic and most appropriate therapy for this neoplasia.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Background: Penile carcinoma (PeCa) is frequently associated with high morbidity rates. Unlikely of the vast majority of tumors, there is no molecular markers described that are able to assist in diagnosis and prognosis or with potential to be therapeutic targets in PeCa. Patients and methods: DNA methylation status (244K Human DNA Methylation Microarray platform, Agilent Technologies) and large-scale expression analysis (4x44K Whole Human Genome Microarray, Agilent Technologies) were performed in 35 and 37 PeCa, respectively. Quantitative bisulfite pyrosequencing (qBP) and RT-qPCR were used to validate the findings in 93 samples. HPV status was assessed using the Linear Array HPV Genotyping kit (Roche Molecular Diagnostics, CA, USA). Results: Methylome analysis revealed 171 hypermethylated and 449 hypomethylated CpGs sites and the transcriptome profiling showed 2986 down- and 2817 over-expressed genes. HPV positivity was found in 32.7% of the cases, mainly the HPV16. The integrative analysis in 32 PeCa revealed a panel of 96 genes with inverse correlation between methylation and gene expression levels. The CpG hypermetlylation and gene downexpression, was confirmed for TWIST1, RSOP2, SOX3, SOX17, CD133, OTX2, HOXA3 and MEIS. In addition, BIRC5, DNMT1 and DNMT3B presented low levels of methylation and overexpression. The comparison of the results with clinical findings revealed that LIN28A, NKX2.2, NKX2.3, LHX5, BDNF, FOXA1 and CDX2 were associated with poor prognosis features. Conclusion: Putative prognostic markers were detected revealing that DNA methylation modulates the expression of several genes in PeCa. These data may prove instrumental for biomarker discovery in clinics and molecular epidemiology of PeCa.