RESUMEN
BACKGROUND: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. METHODS: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. RESULTS: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012). CONCLUSION: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.
Asunto(s)
Recien Nacido Prematuro , Proteínas de la Membrana/genética , Infecciones por Virus Sincitial Respiratorio/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Tiempo de Internación , Mapas de Interacción de Proteínas , Respiración ArtificialRESUMEN
Accurate biomarkers to predict the genesis and progression of pancreatic adenocarcinoma (PAAD) are needed in the fight against this deadly disease. Here, we combined multiple datasets (GEO, TCGA and GTEx) to conduct a comprehensive analysis of pancreatic cancer. Through an in-depth analysis, we discovered that the expression of the gene encoding interferon alpha-inducible protein 27 (IFI27) was significantly higher in pancreatic cancer tissues than that in normal tissues, and that higher expression of IFI27 was negatively correlated with the overall survival rate of pancreatic cancer patients. The functional annotation of IFI27 demonstrated relationships to cellular immunity and metabolism, especially glycolysis. Analysis of infiltrating immune cells displayed that higher expression of IFI27 expression correlates with decreased CD8 + T cells and increased M2 macrophages in the tumor immune microenvironment (TIME), then biochemical analyses of a mouse model and immunohistochemical (IHC) staining verified that glycolytic enzymes and M2 macrophages increased significantly in pancreatic cancer tissues. We speculate that IFI27 may affect the tumor microenvironment (TME) of PAAD by regulating cellular immunity and metabolism, thereby promoting the progression of pancreatic carcinoma and worsening the prognosis. These findings of our present study are solid evidence that IFI27 is a potential prognostic biomarker of pancreatic cancer and that it affects the tumor immune microenvironment.
Asunto(s)
Biomarcadores de Tumor , Proteínas de la Membrana , Neoplasias Pancreáticas , Transcriptoma/genética , Microambiente Tumoral , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biología Computacional , Femenino , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Interferon alpha-inducible protein 27 (IFI27) is a newly discovered protein that participates in biological functions such as apoptosis,cell autophagy,oncolytic and immunoregulation.It also plays a major role in promoting tumor development,such as in breast cancer,ovarian cancer,liver cancer,squamous cell carcinoma and so on.Besides,studies have shown that IFI27 can interact with signal transducer and activator of transcription 1,microRNAs,interferon regulatory factor 4 and other genes,which promotes the development of tumors.Therefore,IFI27 is expected to be a marker for the occurrence and development of tumors,providing a new target for cancer therapy.