Targeted immune response gene expression profiles linked with necrosis and mortality in preterm infants with surgical necrotizing enterocolitis

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Background We sought to determine changes in the expression of immune response-related genes occurring in surgical necrotizing enterocolitis (NEC) tissues from infants with necrosis severity and survival status. Methods Targeted RNA sequencing of a select panel of 395 immune response genes was performed on RNA isolated from formalin-fixed, paraffin-embedded 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 after correcting for RNA integrity. Results Thirty-five genes were differentially expressed (FDR-adjusted p <0.1) between mild-moderate necrosis and severe necrosis. Principal component analysis identified alternations in genes involved in host defense, natural killer (NK) cell signaling and development, and apoptosis which were overexpressed in severe necrosis ( IGJ , GZMA , TNFSF10 , KLRB1 , and CD160 ). Expression of leukocyte antigens ( ITGAM , ITGAX ) and cytokine and chemokine receptors (such as IL1A , IL1B , CCL2 , CCL3 ) was increased in patients with mild necrosis. Six genes were significantly differentially expressed (FDR-adjusted p <0.1) between survivors and the non-survivors. Genes related to chemokine neutrophil attractants ( CXCL1 , GBP , PTGS2 , CXCL11 , CXCL9 , and CXCL10 ) were upregulated in non-survivors. Conclusion Severe necrosis and non-survival in NEC infants were associated with differential gene expression related to host defense, NK cell signaling and development, and apoptosis. Understanding the role of these pathways in severe NEC may guide the development of prognostic and treatment pathways.

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