A Glutamine metabolism-related genes prognosis biomarker for predicting prognosis in colorectal carcinoma

Abstract Background Colorectal cancer (CRC) is one of the most common types of tumor in the gastrointestinal tract worldwide. Amino acid metabolism is closely associated with malignant tumor development, infiltration, metastasis and recurrence. More studies are needed to understand the relationship between glutamine metabolic profile and prognosis of colorectal cancer. Methods In our study, we obtained transcriptomic and related clinical information data of CRC patients from The Cancer Genome Atlas (TCGA) database. Consensus clustering analysis was used to classify CRC patients into various molecular subtypes and identify differential expression of genes related to immunity and glutamine metabolism. We applied univariate and multivariate COX regression and lasso regression analyses to construct a risk assessment model incorporating four genes related to glutamine metabolism, and the CRC samples were categorized into high- risk and low-risk groups, and the correlation between the risk model scores and TME, immune cell infiltration, and cellular mutations was investigated. Finally, we validated the correlation of ADIPOQ using immunohistochemistry in colorectal cancer tumor tissues. In addition, this study was externally validated using the GSE39582 dataset from the GEO database. Results By consistent cluster analysis, we identified two different molecular subtypes. It was also found that different GMRG subtypes were associated with patients' clinicopathologic features, prognosis and TME cell infiltration characteristics. Meanwhile, a predictive model on the basis of the GMRGS risk score was developed and the validity of the predictive ability of the model was verified in internal and external datasets. Furthermore, in terms of immune infiltration and cellular mutations, we observed significant variability between high and low risk groups. Conclusion Our study identified four glutamine metabolism-related genes affecting TME, clinicopathological features, immune landscape, and prognosis-related prediction of CRC, and these findings in our study will better understand the mechanisms by which reprogramming of glutamine metabolism is associated with the developmental progression of CRC and will facilitate to improve the treatment of tumors.