Comprehensive Molecular Analyses of Notch Pathway-Related Genes to Predict Prognosis and Immunotherapy Response in Patients with Gastric Cancer.
Yinsen SongNa GaoZhenzhen YangSisen ZhangTianli FanBaojun ZhangPublished in: Journal of oncology (2023)
Gastric cancer (GC) is a highly molecular heterogeneous tumor with unfavorable outcomes. The Notch signaling pathway is an important regulator of immune cell differentiation and has been associated with autoimmune disorders, the development of tumors, and immunomodulation caused by tumors. In this study, by developing a gene signature based on genes relevant to the Notch pathway, we could improve our ability to predict the outcome of patients with GC. From the TCGA database, RNA sequencing data of GC tumors and associated normal tissues were obtained. Microarray data were collected from GEO datasets. The Molecular Signature Database (MSigDB) was accessed in order to retrieve sets of human Notch pathway-related genes (NPRGs). The LASSO analysis performed on the TCGA cohort was used to generate a multigene signature based on prognostic NPRGs. In order to validate the gene signature, the GEO cohort was utilized. Using the CIBERSORT method, we were able to determine the amounts of immune cell infiltration in the GC. In this study, a total of 21 differentially expressed NPRGs were obtained between GC specimens and nontumor specimens. The construction of a prognostic prediction model for patients with GC involved the identification and selection of three different NPRGs. According to the appropriate cutoff value, the patients with GC were divided into two groups: those with a low risk and those with a high risk. The time-dependent ROC curves demonstrated that the new model had satisfactory performance when it came to prognostic prediction. Multivariate assays confirmed that the risk score was an independent marker that may be used to predict the outcome of GC. In addition, the generated nomogram demonstrated a high level of predictive usefulness. Moreover, the scores of immunological infiltration of the majority of immune cells were distinctly different between the two groups, and the low-risk group responded to immunotherapy in a significantly greater degree. According to the results of a functional enrichment study of candidate genes, there are multiple pathways and processes associated with cancer. Taken together, a new gene model associated with the Notch pathway may be utilized for the purpose of predicting the prognosis of GC. One potential method of treatment for GC is to focus on NPRGs.
Keyphrases
- gas chromatography
- signaling pathway
- cell proliferation
- genome wide
- gene expression
- mass spectrometry
- type diabetes
- transcription factor
- machine learning
- genome wide identification
- metabolic syndrome
- adipose tissue
- endothelial cells
- risk assessment
- big data
- emergency department
- epithelial mesenchymal transition
- skeletal muscle
- tandem mass spectrometry
- insulin resistance
- artificial intelligence
- single molecule
- weight loss
- climate change
- ultrasound guided
- childhood cancer