Abstract
BACKGROUND: We aim to determine the gene expression changes that occur in surgical NEC infants with and without moderate to severe necrosis and survivors and non-survivors. METHODS: Targeted RNA sequencing was performed on RNA isolated from formalin-fixed, paraffin-embedded (FFPE) intestinal tissue samples (N=36). DeSeq2 was used to analyze differential expressions between infants with mild to moderate and severe necrosis and with respect to survival status. RESULTS: Thirty-five genes were differentially expressed (FDR- adjusted p < 0.05) between mild-medium necrosis and severe necrosis. Genes involved in altered host defense, natural killer (NK) cell signaling and development, and apoptosis were overexpressed in severe necrosis (IGJ, GZMA, TNFSF10, KLRB1, and CD160). Expression of leukocytes antigens (ITGAM, ITGAX) and cytokine and chemokine receptors (such as IL1A, IL1B, CCL2, CCL3) were increased in patients with mild necrosis. Six genes were significantly differentially expressed (FDR- adjusted p < 0.05) between survivors and the non-survivors. Genes related to chemokines attracting neutrophils (CXCL1, GBP,PTGS2,CXCL11,CXCL9, and CXCL10) were upregulated in non-survivors. CONCLUSION: Severe necrosis and non-survival of NEC infants were associated with differential genes expression related to host defense, NK cell signaling and development, and apoptosis. Understanding these pathways can guide the development of prognostic and treatment pathways.