Identification of common core genes and pathways in childhood sepsis and cancer by bioinformatics analysis.

Abstract

Introduction: Sepsis and cancer are both leading causes of death worldwide, and they share several pathophysiological characteristics. Some studies have suggested a possible association between sepsis and cancer; however, few have investigated the core genes involved in both diseases.

Methods: Core genes common to both sepsis and cancer were identified using pediatric sepsis datasets (GEO: GSE26378, GSE4607, GSE8121 and GSE13904) and cancer databases (TCGA: BRCA, COADREAD, ESCA, KIRC, LIHC, LUAD, STAD). Gene Ontology (GO) and Reactome enrichment analyses, along with a protein-protein interaction (PPI) network analysis, were performed. Pharmacophore screening was applied to predict the targets of oxymatrine and ulinastatin, and potential target genes shared by both cancer and sepsis were identified. Survival analysis was performed. The association between the target genes and tumor size and number of positive lymph nodes was investigated by Pearson correlation analysis. The association between the target genes and tumor stage was investigated by Fisher's exact test. Molecular docking analysis was performed to evaluate the affinity of the candidate drugs for their targets.

Results: A total of 641 common genes were identified. GO enrichment analysis showed that common genes were enriched in neutrophil degranulation, inflammatory response and innate immune response. Reactome enrichment analysis showed that common genes were enriched in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, transcriptional regulation of granulopoiesis and interleukin-10 signaling. The PPI network showed that the top 10 core genes were TLR4, IL1B, IL10, ITGAM, TLR2, PTPRC, CDK1, FOS, MMP9 and ITGB2. The survival analysis showed that the high expression of BCAT1, CSAD, G6PD, GM2A, MMP9, PYGL and TOP2A was associated with poorer prognosis in several cancers. Molecular docking showed that oxymatrine and ulinastatin can bind to protein targets with highly stable binding.

Conclusions: We identified genes with common effects on both childhood sepsis and cancer, which provides new insights into the association between sepsis and cancer. In addition, two drugs with potential clinical application value were identified. Further studies are required to validate the role of these common core genes in sepsis and cancer and to evaluate the potential utility of these drugs.