Identificação e caracterização de possiveis marcadores moleculares em carcinoma renal de células claras
Arquivos
Data
2009-02-19
Autores
Pires, Lilian Campos [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os dados de seqüência genômicas humanas depositados em bancos públicos têm fornecido uma oportunidade sem precedentes para pesquisadores decifrarem a funcionalidade do genoma humano. Essas informações são extremamente valiosas na prevenção, diagnóstico e tratamento do câncer. O Cancer Genome Anatomy Project (CGAP), o Gene Expression Omnibus (GEO), o Genome Data Mining (GDM) e o Babelomics funtional analysis of genome-scale experiments representam quatro importantes ferramentas para o estudo da genética funcional. O objetivo do presente trabalho foi o de explorar bancos de dados públicos para selecionar e validar a expressão de genes relacionados com o desenvolvimento e a progressão de carcinoma renal de células claras (CRcc). Utilizando ferramentas de bioinformática foi analisada a expressão gênica diferencial entre duas bibliotecas de SAGE elaboradas a partir de tecidos renais normais e de CRcc. Os resultados obtidos demonstraram alterações na expressão de genes participantes de importantes vias metabólicas. Baseando-se nessas análises, os genes CDK7, CLDN1, CSTB, EPC2 e ZNF706 foram selecionados e a expressão gênica diferencial desses foi avaliada por PCR em tempo real em 35 amostras de pacientes portadores de CRcc em diferentes estágios de progressão da doença e 1 amostra metastática. Paralelamente, utilizando-se a metodologia de RaSH foram elaboradas bibliotecas subtrativas entre o tecido neoplásico e o tecidos normal, sendo selecionados os genes MATR3 e PITPNB. O ZNF706 apresentou super expressão em relação aos tecidos normais, nas amostras tumorais analisadas independentemente do grau de evolução tumoral. O mesmo comportamento foi apresentado pelo gene CSTB, sendo que os maiores níveis de expressão foram observados nas amostras de estágio III de progressão tumoral. O gene CDK7 apresentou níveis de expressão dependente do grau de evolução da...
The data of human genomic sequences available in public database have provided an unpredictable opportunity for researchers to decipher the utility of human genome. This information is extremely valuable in prevention, diagnosis and cancer treatment. The Cancer Genome Anatomy Project (CGAP), the Gene expression Omnibus (GEO), the Genome Data Mining (GDM) and the Babelomics Functional Analysis of Genome-Scale Experiments do represent four important tools for functional genetics studies. This work aimed to explore public database to select and validate expression of genes related to development and progression of Clear Cell Renal Cell Carcinoma (ccRCC). The differential gene expression of two SAGE libraries from normal renal tissues and ccRCC was analyzed using bioinformatics tools. The results showed altered gene expression pattern in genes that participate in important metabolic pathways. Based on these analysis, the genes CDK7, CLDN1, CSTB, EPC2 and ZNF706 were selected and their differential gene expression was evaluated by Real Time PCR in 35 tissue samples from patients with ccRCC in different stages of disease progression and one metastatic sample. Simultaneously through RaSH methodology were elaborated subtractive libraries between normal and neoplasic tissues so the genes MATR3 and PITPNB were selected. The ZNF706 presented over expression in tumor tissues independent of tumor progression grade. The same behavior was presented by CSTB where the higher expression levels were observed in samples from stage IV of tumor progression. The CDK7 gene presented expression levels dependent of disease evolution grade where the lowers levels were in stages I, II, III and presented over expression in samples from stage IV and retroperitoneal metastasis. This result shows a clear relationship between CDK7 expression and the aggressiveness of ccRCC and suggests that this gene... (Complete abstract click electronic access below)
The data of human genomic sequences available in public database have provided an unpredictable opportunity for researchers to decipher the utility of human genome. This information is extremely valuable in prevention, diagnosis and cancer treatment. The Cancer Genome Anatomy Project (CGAP), the Gene expression Omnibus (GEO), the Genome Data Mining (GDM) and the Babelomics Functional Analysis of Genome-Scale Experiments do represent four important tools for functional genetics studies. This work aimed to explore public database to select and validate expression of genes related to development and progression of Clear Cell Renal Cell Carcinoma (ccRCC). The differential gene expression of two SAGE libraries from normal renal tissues and ccRCC was analyzed using bioinformatics tools. The results showed altered gene expression pattern in genes that participate in important metabolic pathways. Based on these analysis, the genes CDK7, CLDN1, CSTB, EPC2 and ZNF706 were selected and their differential gene expression was evaluated by Real Time PCR in 35 tissue samples from patients with ccRCC in different stages of disease progression and one metastatic sample. Simultaneously through RaSH methodology were elaborated subtractive libraries between normal and neoplasic tissues so the genes MATR3 and PITPNB were selected. The ZNF706 presented over expression in tumor tissues independent of tumor progression grade. The same behavior was presented by CSTB where the higher expression levels were observed in samples from stage IV of tumor progression. The CDK7 gene presented expression levels dependent of disease evolution grade where the lowers levels were in stages I, II, III and presented over expression in samples from stage IV and retroperitoneal metastasis. This result shows a clear relationship between CDK7 expression and the aggressiveness of ccRCC and suggests that this gene... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Cancer - Aspectos geneticos, Expressão gênica, Rins - Câncer, Marcadores biologicos de tumor, Carcinoma renal de células claras, Expressão genética, Clear cell renal cell carcinoma, Gene expression, Molecular markers
Como citar
PIRES, Lilian Campos. Identificação e caracterização de possiveis marcadores moleculares em carcinoma renal de células claras. 2009. 99 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências, Letras e Ciências Exatas, 2009.