Insights into the prognostic value and immunological role of CD74 in pan-cancer

Abstract

Background: CD74 is a non-polymorphic type II transmembrane glycoprotein. It is involved in the regulation of T and B cell development, and dendritic cell (DC) motility. Numerous studies have found that CD74 exerts an essential role in tumor immunity, but the expression profile of CD74 is still not systematically reported, and its value in human pan-cancer analysis is unknown. In this study, we analyzed the expression pattern of CD74 in 33 cancers, and evaluated the significance of CD74 in prognosis prediction and cancer immunity.

Methods: Pan-cancer dataset from UCSC Xena.We used the Sangerbox website combined with R software' Timer, CIBERSORT method and IOBR package to analyze and plot the data. Survival was assessed using the Kaplan-Meier method and log-rank test for 33 cancer types (p < 0.05). In addition, to explore the relationship between CD74 expression and immune checkpoints, immune cell infiltration, tumor mutational burden (TMB) and microsatellite instability (MSI), Spearman correlation analysis was performed.

Results: This study comprehensively analyzed CD74 expression in 33 different tumor types, revealing that CD74 play an crucial role in cancer formation and development.

Conclusions: CD74 gene expression in different cancers is associated with immune cell infiltration and immunomodulators and may provide a promising target for survival and immunotherapy. Our study shows that CD74 has an essential role as a biomarker of prognosis during tumor development, which highlights the possibility of new targeted therapies.

Keywords: CD74; Immune microenvironment; Immunotherapy; Pan-cancer; Prognosis.

Fig. 1

Pan-cancer CD74 and MIF expression. A The mRNA level of CD74 in CCLE. B The expression of CD74 between tumor tissues and normal tissues in TCGA database. C The expression of MIF between tumor tissues and normal tissues. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 2

CD74 expression in colorectal cancer. A The mRNA relative expression level of CD74 in colorectal cancer. B Expression of CD74 protein levels. N1-3 is normal tissue, T1-3 is tumor tissue

Fig. 3

The relationship between the level of CD74 and OS in tumor patients. A OS related forest map. B–J Kaplan—Meier survival curves in UVM, LGG, CESC, BRCA, LAML, LUAD, SKCM, SARC and THYM

Fig. 4

The relationship between the level of CD74 and DSS in tumor patients. A DSS related forest map. B–I Kaplan—Meier survival curves in ACC, LGG, CESC, BRCA, LUAD, THYM, SKCM and UVM

Fig. 5

Association between the CD74 expression and the DFI of cancer patients. A Forest plot of DFI associations in 33 types of tumor. B–D Kaplan–Meier survival curves of DFI for patients stratified by the different expressions of CD74 BLCA, BRCA and LIHC

Fig. 6

Association between the CD74 expression and the PFI of cancer patients. A Forest plot of PFI associations in 33 types of tumor. B–I Kaplan–Meier survival curves of PFI for patients stratified by the different expressions of CD74 GMB, LGG, ACC, BRCA, LUAD, THYM, SKCM, LIHC

Fig. 7

Immune cell infiltration analysis. A CIBERSORT method was used to compare the relationship between CD74 expression and tumor invasion of different immune cells. B MHC, EC, SC, CP, AZ, IPS infiltration score of each tumor was assessed by deconvo_ips method. The asterisks indicate a statistically significant p-value calculated using spearman correlation analysis. *P < 0.05

Fig. 8

The relationship between CD74 expression and ImmuneScore. The results showed that CD74 expression in most tumors was significantly and positively correlated with ImmuneScore

Fig. 9

Correlation between CD74 and 60 immunomodulators (Inhibitory(24)、Stimulatory(36)). The asterisks indicate a statistically significant p-value calculated using spearman correlation analysis. The upper left corner of each square represents the correlation coefficient by color change, and the lower right corner is the p-value by color change; p < 0.05 indicates statistical significance. *P < 0.05

Fig. 10

Associations between CD74 expression and tumor mutational burden (TMB) and microsatellite instability (MSI). A The association between CD74 expression and TMB levels in tumors. B The association between CD74 expression and MSI event in tumors

Fig. 11

Analysis results of GSEA. A HALLMARK analysis of CD74 in LIHC. B GO functional annotation of CD74 in LIHC. C KEGG pathway analysis of CD74 in LIHC. The chart above shows only some of the results. Peaks on the upward curve indicate positive regulation and peaks on the downward curve indicate negative regulation. Here we show only a few of these signaling pathways