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

Abstract

BackgroundStomach 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.MethodsThe 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.ResultsIn 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.ConclusionsNOTCH1 could be a potential target for STAD. The mechanisms underpinning NOTCH1-medicated prognostic values of immune signatures should be further explored.