Pan-Cancer Analysis Reveals NMDA Receptors as Prognostic and Immunotherapy Biomarkers in Cancer Patients

Abstract

N-methyl-D-aspartate (NMDA) receptors, one subtype of ionotropic glutamate receptors, may combine with glutamate to further exert regulatory effects on tumors. This research first analyzed the expression levels of 7 genes expressing NMDA receptor subunits, and found that GRIN2D was expressed at higher levels in most types of tumor, while the other genes expression levels differed little. Prognostic analysis showed that GRIN2D was positively or negatively correlated with the prognosis of various tumor patients. In 14 tumor types, GRIN2D expression was discovered to be related to tumor mutational burden (TMB), and in 7 tumor types, it was strongly related to microsatellite instability (MSI). Analysis of immune cell infiltration level results showed that GRIN2D was correlated with various immune cells, especially T cells, T cells regulatory (Tregs) and tumor-associated macrophages, and GRIN2D was associated to immune score in 14 different tumor types by tumor microenvironment analysis. The study found two tumors more associated with GRIN2D, kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC), for which NMDA receptors might be more significant for their diagnosis, prognosis and immunotherapy. Furthermore, enrichment analysis of GRIN2D revealed that some immune processes were activated. According to the drug sensitivity analysis, GRIN2D was sensitive to 34 drugs, and it might be a potential target of these drugs against tumors. These studies suggested that GRIN2D was used as a potential tumor marker to evaluate the prognosis of tumor patients and might become a key immunomodulatory target in tumor progression.