Abstract
Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment.Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis.Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival.Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.
Highlights
Gliomas are primary tumors derived from the glial cells in the central nervous system, which comprise about 80% of malignant brain tumors (Goodenberger and Jenkins, 2012)
In both lower-grade glioma (LGG) and GBM, the expression of Cluster of differentiation 74 (CD74) was significantly higher compared to the normal tissue (p < 0.05) (Figure 1A)
Kruskal-Wallis test revealed that the expression of CD74 was significantly elevated in grade IV glioma compared with grade II and III gliomas in the The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), CGGA301, and GSE108474 datasets (p < 0.05) (Figure 1B)
Summary
Gliomas are primary tumors derived from the glial cells in the central nervous system, which comprise about 80% of malignant brain tumors (Goodenberger and Jenkins, 2012). Great progress has been achieved to develop novel strategies for the treatment of cancers, the prognosis of glioma patients remains unsatisfactory. Several biomarkers have been found to predict the prognoses of glioma patients with potent value. Since the prognosis of glioma patients remains poor, more biomarkers are needed to predict the survival of glioma patients. Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. These studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment
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