Molecular subtypes based on the expression of glutamine metabolism-related genes predict prognosis, tumor microenvironment, and drug therapy response of colon adenocarcinoma.

Abstract

Background and study aims: Glutamine metabolism (GM) plays an instrumental role in the occurrence and progression of tumors. However, the characteristics of glutamine metabolism-related genes (GMRGs) in colon adenocarcinoma (COAD) have not been elucidated. This project aims to dig out the role of GMRGs in COAD molecular subtypes, prognosis, and tumor microenvironment (TME) to proffer a scientific foundation for the evaluation of COAD prognosis and mechanism research.

Material and methods: Disease data of COAD (including clinical information and gene expression data) and GMRG data were collected from The Cancer Genome Atlas (TCGA)-COAD. GMRGs in COAD were obtained through differential analysis, cluster analysis, protein-protein interaction (PPI) network analysis, and regression analysis for setting up a prognostic model. Disease information was collected from GSE29621 to validate the model. Differences in immunotherapy response and drug sensitivity among high-Riskscore (HR) and low-Riskscore (LR) groups were evaluated.

Results: 45 GMRGs associated with COAD survival rate were identified through univariate analysis. Cluster and survival analyses revealed that these genes could cluster the COAD population into two clusters with great survival differences. A risk model with 10 feature genes was established through regression analysis. Prediction of immunotherapy sensitivity uncovered that the LR group was more sensitive to immunotherapy.

Conclusion: In summary, this project set up a reliable prognostic risk model with GMRGs, which can proffer a feasible basis for the study of prognosis and related mechanisms in COAD.