Transcriptome Analysis of Premature Infants with Necrotizing Enterocolitis (NEC)
Necrotizing enterocolitis (NEC) is one of the most common and destructive newborn and premature diseases requiring emergent gastrointestinal surgical intervention. The etiology and molecular pathology of NEC with a high rate of mortality and morbidity remain unknown. Here, we aim to analyze the global gene expression pattern of NEC patients via a high-throughput sequencing approach. 11 premature NEC patients fit the inclusion and exclusion criteria and were subjected to RNA sequencing analyses. Compared to the healthy reference, a total of 1,204 Differentially Expressed Genes (DEG) were detected in NEC patients, of which 636 were up and 568 were found to be down-regulated. We measured elevated expression of the hypoxia-induced apoptosis related genes HIF1AAS3, HIF1AAS1, such caspase cascade related genes as BCL2, BCL6, CASP5, CASP7 and inflammation associated genes as IL1RAP, IL6ST, TNFAIP3, TNFRSF10A, TLR6, TLR10. Albeit, down-regulation in the expression level of such genes was observed as IL18, to program the inflammation. Moreover, interestingly, we detected the suppression of the gene expression related to the selenium deficiency for GPX1, GPX4, SELENONI, SELENOM, SELENOF, SELENOW, SELENOT genes. Gene ontology and pathway analyses show that the DEGs are regulated to reflect hypoxia exposure, uncontrolled inflammation, coagulation disorder, impaired antimicrobial activity, mitochondrial dysfunction, autophagy activation, selenium deficiency, and apoptosis induction. These findings provide us with a better understanding of the molecular basis of pathophysiological events leading NEC in premature infants.