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 β1 x 1 + β2 x 2 +... + β ixi . 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.