RESUMO
Alterations in signaling pathways and modulation of cell metabolism are associated with the pathogenesis of cancers, including hepatocellular carcinoma (HCC). Small ubiquitin-like modifier (SUMO) proteins and NF-κB family play major roles in various cellular processes. The current study aims to determine the expression profile of SUMO and NF-κB genes in HCC tumors and investigate their association with the clinical outcome of HCC. The expression of 5 genes - SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 - was quantified in tumor and adjacent non-tumor tissues of 58 HBV-related HCC patients by real-time quantitative PCR and was analyzed for the possible association with clinical parameters of HCC. The expression of SUMO2 was significantly higher in HCC tumor tissues compared to the adjacent non-tumor tissues (Pâ =â .01), while no significant difference in SUMO1, SUMO3, NF-κB p65, and NF-κB p50 expression was observed between HCC tumor and non-tumor tissues (Pâ >â .05). In HCC tissues, a strong correlation was observed between the expression of SUMO2 and NF-κB p50, between SUMO3 and NF-κB p50, between SUMO3 and NF-κB p65 (Spearman rhoâ =â 0.83; 0.82; 0.772 respectively; Pâ <â .001). The expression of SUMO1, SUMO2, SUMO3, NF-κB p65, and NF-κB p50 was decreased in grade 3 compared to grades 1 and 2 in HCC tumors according to the World Health Organization grades system. Our results highlighted that the SUMO2 gene is upregulated in tumor tissues of patients with HCC, and is related to the development of HCC, thus it may be associated with the pathogenesis of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina , Humanos , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteína SUMO-1/genética , Proteína SUMO-1/metabolismo , NF-kappa B/metabolismo , Adulto , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Vírus da Hepatite B/genética , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Idoso , Regulação Neoplásica da Expressão Gênica , Ubiquitinas/genética , Ubiquitinas/metabolismo , Hepatite B/complicações , Hepatite B/genéticaRESUMO
The pathological outcome of dengue disease results from complex interactions between dengue virus (DENV) and host genetics and immune response. Complement receptor types 1 and 2 (CR1 and CR2) mediate complement activation through the alternative pathway. This study investigated the possible association of genetic polymorphisms and plasma levels of CR1 and CR2 with dengue disease. A total of 267 dengue patients and 133 healthy controls were recruited for this study. CR1 and CR2 gene polymorphisms were analyzed by Sanger sequencing, while plasma CR1 and CR2 levels were measured by ELISA. The frequency of the CR1 minor allele rs6691117G was lower in dengue patients and those with severe dengue compared to healthy controls. Plasma CR1 and CR2 levels were decreased in dengue patients compared to healthy controls (P < 0.0001) and were associated with platelet counts. CR1 levels were lower in dengue patients with warning signs (DWS) compared to those without DWS, while CR2 levels were decreased according to the severity of the disease and after 5 days (T1) and 8 days (T2) of follow-up. CR2 levels were decreased in dengue patients positive for anti-DENV IgG and IgM and patients with bleeding and could discriminate DWS and SD from dengue fever patients (AUC = 0.66). In conclusion, this study revealed a reduction in CR2 levels in dengue patients and that the CR1 SNP rs6691117A/G is associated with the dengue severity. The correlation of CR2 levels with platelet counts suggests that CR2 could be an additional biomarker for the prognosis of severe dengue disease.
Assuntos
Receptores de Complemento 3d , Dengue Grave , Humanos , Proteínas Sanguíneas , Gravidade do Paciente , Polimorfismo Genético , Receptores de Complemento/metabolismo , Receptores de Complemento 3b/genética , Dengue Grave/genéticaRESUMO
Aim: The current study investigated the plasma levels of angiopoietin-1/-2 and their association with clinical outcomes of sepsis. Methods: Angiopoietin-1 and -2 levels were quantified in plasma from 105 patients with severe sepsis by ELISA. Results: Angiopoietin-2 levels elevated according to the severity of sepsis progression. Angiopoietin-2 levels were correlated with mean arterial pressure and platelets counts, total bilirubin, creatinine, procalcitonin, lactate levels and SOFA score. Angiopoietin-2 levels accurately discriminated for sepsis with an AUC = 0.97 and septic shock from severe sepsis patients (AUC = 0.778). Conclusion: Plasma angiopoietin-2 levels may serve as an additional biomarker for severe sepsis and septic shock.
The study investigated the plasma levels of angiopoietin-1/-2 and their association with clinical outcomes of sepsis in plasma from 105 patients with severe sepsis by ELISA. The results showed that angiopoietin-2 levels elevated according to the severity of sepsis progression and were correlated with important clinical parameters such as mean arterial pressure and platelets counts, procalcitonin, lactate levels and SOFA score. Angiopoietin-2 levels accurately discriminated for sepsis and septic shock. Thus, plasma angiopoietin-2 levels may serve as an additional biomarker for severe sepsis and septic shock.
