(1415) Identification of Common Core Genes and Pathways of Sepsis and Cancer by Bioinformatics Analysis

Introduction: Both sepsis and cancer are leading causes of death worldwide, and they share a number of pathophysiological features. Some studies have suggested a possible association between sepsis and cancer, but few studied core genes in both diseases.

Methods: Common core genes were identified from sepsis datasets (GEO: GSE26378, GSE4607, GSE8121 and GSE13904) and cancer databases (TCGA: BRCA, COADREAD, ESCA, KIRC, LIHC, LUAD, STAD). Then, GO and Reactome enrichment analyses and PPI network analysis were performed. The pharmacophore screening was used to predict the target of oxymatrine and ulinastatin and potential target genes in both cancer and sepsis were obtained. The 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 exact test. The molecular docking analysis was performed to evaluate the affinity of the candidate drugs for their targets.

Results: In total, 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. 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. The molecular docking showed that oxymatrine and ulinastatin can bind to the protein targets with highly stable binding.

Conclusions: We identified genes with common effects on both 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.