RESUMO
BACKGROUND We aimed to identify pivotal genes and pathways involved in pancreatic ductal adenocarcinoma (PDAC), and explore possible molecular markers for the early diagnosis of the disease. MATERIAL AND METHODS The array data of GSE74629, including 34 PDAC samples and 16 healthy samples, was downloaded from GEO (Gene Expression Omnibus) database. Then, the DEGs (differentially expressed genes) in PDAC samples were compared with healthy samples using limma (linear models for microarray). Gene functional interaction networks were analyzed with Cytoscape and ReactomeFIViz. PPI networks were constructed with Cytoscape software. In addition, PPI (protein-protein interaction) network clustering modules were analyzed with ClusterONE, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses for modules were performed. RESULTS A total of 630 upregulated and 1,002 downregulated DEGs were identified in PDAC samples compared with healthy samples. Some ribosomal protein genes with higher average correlation in module 0 were enriched in the ribosome pathway. NUP107 (nucleoporin 107 kDa) and NUP160 (nucleoporin 160 kDa) were enriched in module 3. HNRNPU (heterogeneous nuclear ribonucleoprotein U) with higher average correlation in module 8 was enriched in the spliceosome pathway. The ribosome pathway and the spliceosome pathway were significantly enriched in cluster 1 and cluster 2, respectively. CONCLUSIONS Ribosomal protein genes Nup170, Nup160, and HNRNPU, and the ribosome pathway as well as the spliceosome pathway may play important roles in PDAC progression. In addition, ribosomal protein genes Nup170, Nup160, and HNRNPU may be used as possible molecular markers for the early diagnosis of the disease.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/diagnóstico , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Biologia Computacional/métodos , Redes de Comunicação de Computadores , Bases de Dados Genéticas , Regulação para Baixo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de Proteínas , Transdução de Sinais/genética , Software , Regulação para CimaRESUMO
SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. SENP2 has been reported to play a critical role in the control of hepatocellular carcinoma (HCC) cell growth by modulating the stability of ß-catenin. However, the underlying mechanism remains largely unknown. Here, we show that the WW domain-containing oxidoreductase (WWOX), a novel inhibitor of the Wnt/ß-catenin pathway, is required for stabilization of ß-catenin regulated by SENP2 in HCC cells. The transcriptional level of WWOX is tightly regulated by SENP2. Moreover, knockdown of WWOX by siRNA attuned SENP2-induced ß-catenin degradation and decreased SENP2-mediated HCC cell proliferation arrest. Taken together, our data suggested that WWOX is a key downstream modulator of the SENP2 tumor suppressor function in HCC cell.
Assuntos
Carcinoma Hepatocelular/metabolismo , Cisteína Endopeptidases/metabolismo , Neoplasias Hepáticas/metabolismo , Oxirredutases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , beta Catenina/metabolismo , Western Blotting , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Oxidorredutase com Domínios WWRESUMO
AIMS: The aim of this study is to evaluate the therapeutic efficacy of Appleby operation for carcinoma of the body and tail of pancreas. MATERIALS AND METHODS: From March 2010 to February 2015, Appleby operation was performed in 17 patients with carcinoma of the body and tail of pancreas. The values of fasting plasma blood, body weight (BW), visual analog pain intensity scale (VAS score), and the quality of life indices were evaluated before and 1 day, 1, 2, 6 weeks after surgery. Survival time, tumor recurrence time, hospitalization time, and treatment-related complications were analyzed. RESULTS: There was no hospital mortality. Pancreatic fistula and diarrhea were major and most frequent. The rate of morbidity in general was 47.1%. After operation, all of the patients were completely pain-free. The VAS score decreased more after surgery comparing with before (83.2 ± 8.5 vs. 1.9 ± 3.6, P < 0.05). After operation, patients gained more than their preoperative BW with a mean increment of (4.1 ± 1.3 kg) (68.1 ± 4.3 vs. 64.0 ± 6.7, P < 0.05). A significant rise of the overall quality of life index was observed after surgery (93.8 ± 9.7 vs. 68.6 ± 6.7, P < 0.05). The 1-, 2-, 3-, and 5-year recurrence rates were 22.9%, 58.9%, 72.6%, and 72.6%, respectively. The 1-, 2-, 3-, and 5-year survival rates after operation were 80.4%, 54.2%, 32.5%, and 16.3%, respectively. CONCLUSIONS: Appleby operation is both safe and effective with regard to pain relief and improvement of overall quality of life. Appleby operation can also achieve a high survival rate and a long overall survival time.
Assuntos
Carcinoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: MicroRNAs (miRNAs) play key roles in tumor development and progression. The aim of this study was to explore the expression levels of miR-34a and miR-217 in hepatocellular carcinoma (HCC) and to further investigate the clinicopathological and prognostic value of miR-34a and miR-217. METHODS: The expression levels of miR-34a and miR-217 were evaluated using quantitative real-time PCR (qRT-PCR). Associations between these miRNAs expression and clinicopathological features were analyzed. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. RESULTS: We found that miR-34a expression was significantly downregulated in HCC tissues (P<0.05). Reduced expression of miR-34a was associated with vascular invasion, and advanced TNM stage (P<0.05). Kaplan-Meier revealed that reduced expression of miR-34a was associated with poor overall survival (log-rank test, P<0.05). We found that miR-217 was downregulated in HCC tissues. Decreased expression of miR-217 was remarkably correlated vascular invasion, and advanced TNM stage (P<0.05). Kaplan-Meier analysis and log-rank test showed that HCC patients with low expression of miR-217 was associated with shorter overall survival than patients with high expression (log-rank test, P<0.05). CONCLUSIONS: Our data showed that downregulation of miR-34a and miR-217 was associated with HCC progression and both of them may act as tumor suppressor in HCC.