Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps.

ABSTRACT

Purpose: This study identified subtypes and prognostic signature of stage I and stage II gastric cancer based on neutrophil extracellular trap (NET)-related genes. Methods: The gene expression data associated with stage I and stage II gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. NET-related genes were obtained from previous reference. Differentially expressed NET-related genes were selected by consensus cluster analysis. The differences in immune infiltration between two subtypes were analyzed. Prognosis-related genes were further screened by univariate Cox regression analysis. Gene Set Enrichment Analysis (GSEA) of prognostic signatures was conducted with clusterprofiler. Finally, a miRNA-mRNA-transcription factor (TF) network was constructed. Results: Total 43 differential NET-related genes were obtained and two subtypes were obtained based on these genes. Patients of cluster 2 had a better prognosis compared to cluster 1. Eight types of immune cells were differential in infiltration level between two subtypes. Following univariate Cox regression analysis, two genes of CXC chemokine receptor 4 (CXCR4) and nuclear factor, erythroid 2-like 2 (NFE2L2) significantly related to patient survival were selected. GSEA of single gene revealed that CXCR4 was associated with allograft rejection and NFE2L2 was associated with drug metabolism-cytochrome P450. A network with 421 miRNA-mRNA-TF regulatory pairs was constructed. Conclusion: The present study identified two subtypes and a prognostic signature for stage I and stage II gastric cancer based on NET-related genes.