MicroRNoma dos carcinomas de fígado
Carregando...
Data
2017-02-21
Autores
Ariede, Jovita Ramos [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Introdução: O carcinoma hepatocelular (CHC) está entre as neoplasias de alta complexidade no diagnóstico, determinação do prognóstico e tratamento, sendo o sexto tipo de câncer mais comum no mundo e a segunda causa mais comum de morte por câncer. Uma variedade de genes alterados foram relatados, revelando heterogeneidade genética entre tumores de diferentes pacientes. Portanto, o insucesso terapêutico da terapia convencional pode ser parcialmente atribuído a essa heterogeneidade associada ao comportamento biológico tumoral. Sendo assim, justifica-se a necessidade de identificação de vias moleculares as quais podem conter biomarcadores clinicamente aplicáveis para a melhoria do diagnóstico e tratamento dos pacientes com CHC. Os resultados podem ter futuras aplicações clínicas utilizando miRNAs e os genes-alvo regulados por miRNAs como biomarcadores com valor diagnóstico, prognóstico e terapêutico. Objetivos: Identificar o perfil global de expressão de miRNAs (microRNoma) e os mRNAs-alvo potencialmente regulados por miRNAs em CHC. Pacientes e Métodos: Foram incluídas 18 amostras de tecido, fixadas em formalina e emblocadas em parafina (FFPE) de carcinoma hepatocelular, sendo 18 amostras tumorais e 18 amostras de tecido hepático histologicamente normal, adjacente ao tumor, dos mesmos pacientes. O perfil de expressão de miRNAs das amostras tumorais foi determinado utilizando o ensaio TaqMan Array Human MicroRAN Cards (TLDA) (card A) (Life Technologies). A análise dos dados utilizou o programa ExpressionSuite v1.0.3. Análises computacionais utilizando algoritmo de bioinformática foram realizadas com o objetivo de identificar genes-alvo regulados por miRNAs, bem como redes de interação proteica e vias moleculares envolvendo genes e miRNAs. Resultados: Foram identificados 8 miRNAs com expressão diferencial estatisticamente significativa (FC ≥1,5 e p <0,05) em carcinoma hepatocelular, sendo que 5 miRNAs estavam com expressão aumentada e 3 miRNAs estavam com expressão diminuída comparado com os tecidos histologicamente normais. Nossos resultados mostram uma complexidade de alterações associadas à tumorigênese do CHC, devido ao número de genes-alvo identificados regulados pelos miRNAs alterados nesse tumor.Conclusão: Redes de interação entre miRNAs e mRNAs-alvo estão associadas ao desenvolvimento e progressão do CHC.
Introduction: Hepatocellular carcinoma (HCC) is among the most complex neoplasms in diagnosis, prognosis, and treatment, being the sixth most common cancer and the second most common cause of cancer death worldwide. Several genes have been reported as deregulated in HCC, revealing the genetic heterogeneity among tumors from different patients. Therefore, treatment failure by conventional therapy may be partially attributed to such heterogeneity associated with tumor biological behavior. Thus, the need for identification of molecular pathways which may contain clinically applicable biomarkers for better diagnosis and treatment of HCC patients is warranted. The results may have future clinical applications using miRNAs and target genes regulated by miRNAs as biomarkers with diagnostic, prognostic and therapeutic value. Objectives: To identify the global expression profile of miRNAs (microRNome) and target mRNAs potentially regulated by miRNAs in HCC. Patients and Methods: Thirty-six formalin-fixed and paraffin-embedded tissue samples (FFPE) from hepatocellular carcinoma were included, with 18 tumor samples and 18 histologically normal hepatic tissue samples adjacent to the tumor from the same patients. miRNA expression profiles were determined using the TaqMan Array Human MicroRNA Cards (TLDA) assay (card A) (Life Technologies). Data analysis used ExpressionSuite v1.0.3 program. Computational bioinformatic analyzes were performed to identify target genes regulated by miRNAs, as well as miRNA-mRNA interaction networks and gateways involving genes and miRNAs. Results: 8 statistically significantly deregulated miRNAs (FC ≥1.5 and p <0.05) were identified in hepatocellular carcinoma, being 5 over-expressed and 3 under-expressed compared to histologically normal liver tissues. Our results showed a complexity of alterations associated with HCC tumorigenesis due to the number of target genes identified by deregulated miRNAs.Conclusion: miRNA-mRNA networks are involved in molecular pathways associated with HCC development and progression.
Introduction: Hepatocellular carcinoma (HCC) is among the most complex neoplasms in diagnosis, prognosis, and treatment, being the sixth most common cancer and the second most common cause of cancer death worldwide. Several genes have been reported as deregulated in HCC, revealing the genetic heterogeneity among tumors from different patients. Therefore, treatment failure by conventional therapy may be partially attributed to such heterogeneity associated with tumor biological behavior. Thus, the need for identification of molecular pathways which may contain clinically applicable biomarkers for better diagnosis and treatment of HCC patients is warranted. The results may have future clinical applications using miRNAs and target genes regulated by miRNAs as biomarkers with diagnostic, prognostic and therapeutic value. Objectives: To identify the global expression profile of miRNAs (microRNome) and target mRNAs potentially regulated by miRNAs in HCC. Patients and Methods: Thirty-six formalin-fixed and paraffin-embedded tissue samples (FFPE) from hepatocellular carcinoma were included, with 18 tumor samples and 18 histologically normal hepatic tissue samples adjacent to the tumor from the same patients. miRNA expression profiles were determined using the TaqMan Array Human MicroRNA Cards (TLDA) assay (card A) (Life Technologies). Data analysis used ExpressionSuite v1.0.3 program. Computational bioinformatic analyzes were performed to identify target genes regulated by miRNAs, as well as miRNA-mRNA interaction networks and gateways involving genes and miRNAs. Results: 8 statistically significantly deregulated miRNAs (FC ≥1.5 and p <0.05) were identified in hepatocellular carcinoma, being 5 over-expressed and 3 under-expressed compared to histologically normal liver tissues. Our results showed a complexity of alterations associated with HCC tumorigenesis due to the number of target genes identified by deregulated miRNAs.Conclusion: miRNA-mRNA networks are involved in molecular pathways associated with HCC development and progression.
Descrição
Palavras-chave
Carcinoma hepatocelular, Biomarcadores, Alvos moleculares terapêuticos, Hepatocellular Carcinoma, Biomarkers, Therapeutic molecular targets, MicroRNA