Construction of a Six-Gene Prognostic Signature Associated with Notch Signaling Pathway in Gastric Cancer

Objective: The Notch signaling pathway plays a key role in the tumor microenvironment. Activation of the Notch signaling path-way promotes the progression of gastric cancer. However, the role of Notch pathway genes in the immune microenvironment and the prognosis of gastric cancer remains unclear. This study aimed to investigate the effect of Notch pathway genes on clinical survival and the immune microenvironment in gastric cancer. Methods: The Cancer Genome Atlas stomach adenocarcinoma and GSE84437 datasets were downloaded. Notch pathway genes were extracted from the databases, and their expression levels between gastric cancer and normal groups were compared. Using univariate and multivariate Cox regression analyses, a risk score model was constructed, and the samples were divided into high-and low-risk groups. A nomogram model was constructed. The mutation frequency, immune cell infiltration, drug sensitivity, and response to immune checkpoint blockade were compared between the different risk groups. Results: Six Notch signaling pathway genes (HEYL, DTX3L, ST3GAL6, FZD7, NOTCH3, and NOTCH4) were selected to con-struct a risk score model. The overall survival in the low-risk group was better than that in the high-risk group. A nomogram constructed based on the American Joint Committee on Cancer stage and risk score could predict 1-, 3-, and 5-year survival rates. Additionally, the altered pathway, mutation pattern, immune microenvironment, drug sensitivity, and response to im-mune checkpoint blockade were significantly different between the two risk groups. Conclusions: The six-gene signature based on the Notch signaling pathway allows the prediction of the prognosis of gastric cancer patients and may prove useful for guiding gastric cancer therapeutic strategies.

Automated summary

This study investigates the effect of Notch pathway genes on clinical survival and the immune microenvironment in gastric cancer. A risk score model and a nomogram model were constructed to predict the survival rates of gastric cancer patients based on the expression of six Notch signaling pathway genes. The different risk groups showed significant differences in mutation frequency, immune cell infiltration, drug sensitivity, and response to immune checkpoint blockade.