Identification of 8-gene risk prediction signature associated with NOTCH1 in stomach adenocarcinoma based on bioinformatics analysis

BACKGROUND: Stomach adenocarcinoma (STAD), is the most common histological type of gastric cancer (GC) with high mortality and poor prognosis. We sought to investigate the contribution of Notch receptor 1 (NOTCH1) to STAD immunity. METHODS: The profiles of immune cells in STAD cohorts were compared, and a correlation analysis between the NOTCH1 gene and tumor immune cell infiltration was then conducted. The immune-related genes (IRGs) associated with the NOTCH1 gene were identified. Based on the NOTCH1-associated IRGs, multiple-gene risk prediction signatures were established. The relationship between the expression levels of the selected IRGs and overall survival (OS) was analyzed by a univariate analysis. The risk score was calculated using the formula of β1x1 + β2x2 +... + βixi. A prognostic nomogram was constructed to predict individuals’ survival probabilities. RESULTS: In STAD, NOTCH1 expression levels were significantly negatively associated with tumor-infiltrating lymphocyte (TIL) Act dendritic cells (DCs) (r=−0.196, P value =6.24e-05), TIL cluster of differentiation (CD) 56 bright cells (r=−0.115, P value =0.0193), TIL immature DCs (r=−0.293, P value =1.16e-09), TIL monocyte cells (r=−0.185, P value =0.000149), TIL central memory T CD4 cells (r=−0.126, P value =0.0103), and TIL gamma delta T cells (r=−0.149, P value =0.00229). The resulting risk scores of the 8-gene risk prediction signature (corticotrophin releasing hormone receptor 2 (CRHR2) (HR =1.858, P value =0.048), fms related receptor tyrosine kinase 1 (FLT1) (HR =1.268, P value =0.048), fms related receptor tyrosine kinase 4 (FLT4) (HR =1.334, P value =0.031), glial fibrillary acidic protein (GFAP) (HR =2.739, P value =0.008), platelet-derived growth factor receptor beta (PDGFRB) (HR =1.192, P value =0.02), prostaglandin D2 receptor (PTGDR) (HR =1.564, P value =0.049), semaphorin 5B (SEMA5B) (HR =1.154, P value =0.029), and tyrosine kinase 2 (TYK2) (HR =0.734, P value =0.041) were independent prognostic predictors for STAD patients. CONCLUSIONS: NOTCH1 could be a potential target for STAD. The mechanisms underpinning NOTCH1-medicated prognostic values of immune signatures should be further explored.