Assinatura gênica relacionada ao metabolismo de heme e hemoglobina na sepse secundária à pneumonia

• Ano de defesa: 2019
• Autor(a) principal: Leite, Giuseppe Gianini Figueirêdo [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Gene Expression Profile; Hemoglobin; Cytoprotection; Outcome; Perfilação Da Expressão Gênica; Hemoglobinas; Citoproteção; Desfecho
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7656547; https://repositorio.unifesp.br/handle/11600/59290

Objective: In the present study we investigated the gene expression profiles of sepsis patients caused by community-acquired pneumonia (CAP) or hospital acquired pneumonia (HAP) and their relation with heme and hemoglobin metabolism. Methods: Three microarray datasets were used: GSE48080 (S1), E-MTAB-5273 (S2) and GSE65682 (S3). Samples from each data set were grouped according to patient outcomes and sample collection day. Samples of each dataset were grouped according to patients’ outcome and each sample collection day. The DEGs lists were obtained using the R package LIMMA. DEGs of the S1 dataset were used to construct and analyze four co-expression networks using GeneMANIA interaction database and Cytoscape. The analysis of the molecular signature related to the heme metabolism was performed using "Gene sets hallmark" present in Molecular Signatures Database v 6.2. Common DEGs between the signatures had their expression analyzed using the Immuno-Navigator database. Results: Through the analysis of networks in the data set S1, we found modules directly related to the heme/hemoglobin biosynthesis pathway present only in the networks of the surviving groups. The heme/hemoglobin metabolism pathway was found to be enriched in the three cohorts of patients, with four related genes (ALAS2, AHSP, HBD and CA1) common to the three datasets. The gene expression of these genes is related to the outcome in in S1 and S2 patients, being more prominent in follow-up samples. The results obtained through the Immuno-Navigator showed a direct and statistically relationship between the expression of these four genes in samples of PBMC and neutrophils. Conclusion: We conclude that the heme/hemoglobin metabolism pathway is up-regulated in sepsis and may represent a protective response of white cells to the hostile environment present in septic patients.