RESUMEN
Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.
Asunto(s)
Enfermedad de Alzheimer , Antígenos CD , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Masculino , Femenino , Anciano , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Cerebelo/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Corteza Auditiva/metabolismo , Precursor de Proteína beta-Amiloide/genética , Anciano de 80 o más Años , Apolipoproteínas E/genética , Expresión Génica/genética , Estudios de Casos y ControlesRESUMEN
PURPOSE: Analyze the expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b in patients with normal gastric tissue, chronic gastritis, and gastric adenocarcinoma. METHODS: The expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b by qRT-PCR was analyzed in 158 samples from 53 patients with normal gastric mucosa, 86 with chronic gastritis, and 19 with gastric cancer. RESULTS: The comparison between the gastric cancer and the control group revealed a decreased expression of caspase-9 in gastric cancer tissues; considering the Helicobacter pylor presence, comparable results were revealed. Smac/DIABLO was increased in gastric cancer cells, while XIAP demonstrated no significant difference in the gene expression. The microRNA analysis revealed a decreased expression of let-7a and let-7b in samples positive to H. pylori infection and in gastric cancer group, regardless of the presence of the bacterium. CONCLUSION: Our study provided some evidence of low activity of the intrinsic apoptosis pathway, as well as the influence of H. pylori on let-7a and let-7b expression.
Asunto(s)
Adenocarcinoma/genética , Apoptosis/genética , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patología , Adulto , Anciano , Proteínas Reguladoras de la Apoptosis/genética , Biopsia , Caspasa 9/genética , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/genética , Gastritis/microbiología , Gastritis/patología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
PURPOSE: The aim of this study was to evaluate the expression of miR-125a-5p in patients with dyspeptic symptoms and gastric cancer, correlating them with the development of this cancer and H. pylori. METHODS: Patients were divided in groups according to histopathological analysis (control, gastritis, and cancer groups). Polymerase chain reaction was performed to detect H. pylori and real-time quantitative PCR to determine miR-125a-5p expression. RESULTS: H. pylori was detected in 44% of the patients, with prevalence in the gastritis and cancer groups. A statistically significant decrease of miR-125a-5p expression was found in the control positive (p = 0.0183*), gastritis positive (p = 0.0380*), and cancer positive (p = 0.0288*) groups when compared with the control negative group. CONCLUSION: We suggest that decreased expression of the miRNA-125a-5p associated with the presence of the H. pylori is an important mechanism in gastric diseases and could be a possible marker for early diagnosis of gastric cancer.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Gastritis/genética , Infecciones por Helicobacter/genética , MicroARNs/metabolismo , Neoplasias Gástricas/genética , Adulto , Anciano , Biomarcadores de Tumor/análisis , Brasil/epidemiología , Línea Celular Tumoral , Proliferación Celular , Detección Precoz del Cáncer/métodos , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/patología , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , MicroARNs/análisis , Persona de Mediana Edad , Prevalencia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
The process of combating neoplasms and mononuclear cells, and during H. pylori infection, several pro-inflammatory and anti-inflammatory cytokines are synthesized. In view of the involvement of the IL-6 law and the presence of H. pylori in the development of gastric diseases, the present study aimed to characterize the promoter-region polymorphism -597 (G/A) (rs1800797), -572 (C/G) (rs1800796), and -174 (G/C) (rs1800795) by PCR-RFLP in 375 gastric biopsy specimens from patients with peptic symptoms. A total of 375 samples were analyzed: 87 patients (without lesion without gastric tissue); 236 patients with gastritis and 52 patients with gastric cancer analyzed the PCR-RFLP techniques. All the results were normalized in relation to the presence of H. pylori. The frequencies of the three polymorphisms were compared in the Control vs Gastritis groups and a statistically significant test observed: -174 (G/C) (OR: 1.27; 95% CI: 0.84-1.93; P = 0.26), 572 (C/G) (OR: 1.42; 95% CI: 0.78-2.59; P = 0.25), and 597 (G/A) (OR: 0.98; 95% CI, 0.64-1.52; P = 0.94). Similar results were obtained when the gastric cancer group was compared to the control group: -174 (G/C) (OR: 1.27; 95% CI: 0.66-2.47; P = 0.47), -572 (C/G) (OR: 1.07; 95% CI: 0.43-2.68; P = 0.88), and -597 (G/A) (OR: 1.01; 95% CI, 0.5-0.9; P = 0.99). The haplotypes were and were not observed statistically significant differences. In conclusion, we found no correlations between any of the three polymorphisms in the IL-6 gene analyzed in this study and a higher risk of gastritis or gastric cancer.
Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/genética , Interleucina-6/genética , Neoplasias Gástricas/genética , Femenino , Estudios de Asociación Genética , Genotipo , Haplotipos/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
Virulence factors of H. pylori, such as outer inflammatory protein A (oipA), are closely involved in the development of gastric diseases such as chronic gastritis and gastric cancer. The functional status of oipA is regulated by a repair mechanism based on CT dinucleotide repeats that influence the reading frame, thus granting the gene a functional or nonfunctional status; in other words, the functional status of the oipA gene seems to be associated with the development of gastric diseases. This study sought to detect the presence of the oipA gene and to determine its functional status in patients with gastric diseases. We analyzed 516 biopsy samples (101 with normal gastric tissue, 365 with chronic gastritis, and 50 with gastric cancer). The presence of oipA was determined by PCR, and the gene status was determined using sequencing reactions. The oipA gene was found to be associated with the development of chronic gastritis, and the "on" status of the gene was the most frequent in patients with gastric cancer who were from Western countries. The CT repeats revealed geographic characteristics, but it is the functional status of the oipA gene that seems to be involved in the development of gastric diseases and in the development of gastric cancer in particular.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/genética , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Sistemas de Lectura/genética , Neoplasias Gástricas/microbiología , Antígenos Bacterianos/genética , Repeticiones de Dinucleótido/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de Virulencia/genéticaRESUMEN
PURPOSE: This study investigated miRNA-181c expression in control patients (healthy gastric mucosa), patients with gastritis, and patients with gastric cancer. The presence of Helicobacter pylori was determined, and the associations between H. pylori infection, levels of miRNA-181c expression, and gastric disease were also analyzed. METHODS: A total of 158 subjects were included in the study, and the three groups were respectively composed of 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. miRNA-181c expression and H. pylori infection were determined by quantitative real-time PCR and PCR, respectively. The subsequent target gene analysis was performed using the bioinformatics approach to understand the possible mechanisms of gastric cancer. RESULTS: We determined significantly lower miRNA-181c expression in the gastric cancer group when compared to the control and gastritis groups, regardless of the presence of H. pylori. There was no difference in miRNA-181c expression between the control group and gastritis group, whether the presence of H. pylori was considered or not. The bioinformatics approach identified several genes as possible targets for miRNA-181c, including the X-linked inhibitor of apoptosis (XIAP) gene (which encodes a protein that belongs to a family of apoptotic suppressor proteins), the caspase 9 gene, and the caspase 3 gene. All target genes identified may be involved in gastric cancer and apoptosis pathways. CONCLUSION: The results suggest that the presence of H. pylori has no influence on microRNA expression and that the downregulation of miR-181c may play an important role in gastric cancer progression by controlling important genes associated with apoptosis. Therefore, miRNA-181c may be a potential marker of gastric cancer.