Biological and immunological significance of DLL3 expression in different tumor tissues: a pan-cancer analysis

Abstract

Objective: To evaluate the biological and immunological significance of DLL3 expression in different tumor tissues and provide insight into the role of DLL3 in tumor immunotherapy.

Material and methods: RNA expression and clinical data of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were acquired, and we employed couple of bioinformatics methods to investigate the potential biological and immunological role DLL3, including pan-cancer expression, survival analysis, GSVA and it's correlation with immune infiltration scores, tumor mutation burden, tumor microsatellite instability.

Results: The findings indicate that DLL3 is expressed in the majority of tumors but is only weakly prevalent in HNSC. In 18 different types of cancers, DLL3 expression was linked to TMB and MSI, whereas in KIRC, LIHC, and PAAD, DLL3 expression and TME were correlated. Additionally, DLL3 gene expression linked positively with M0 and M2 macrophage infiltration levels but negatively with the infiltration of most immune cells. And connection with DLL3 expression varied depending on the kind of T cell. Finally, the GSVA data suggested that DLL3 expression is often unfavorably correlated with most pathways.

Conclusions: DLL3 can be used as a stand-alone prognostic factor for many tumor types, and that the level of its expression will have a different prognostic impact for various tumor types. DLL3 expression across numerous cancer types was related to TMB, MSI, and immune cell infiltration. The role of DLL3 in carcinogenesis may serve as a guide for the creation of future immunotherapies that are more individualized and precise.

Keywords: DLL3; immunity; microsatellite instability; pan-cancer; prognosis.

Figure 1

Differential expression of DLL3. (A) DLL3 expression in 34 types of cancer. (B) Comparison of DLL3 expression between tumor and normal samples. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Association between DLL3 expression and overall survival time in days (OS). (A) Forest plot of OS associations in 34 types of tumor. (B) Kaplan-Meier analysis of the association between DLL3 expression and OS.

Figure 3

Association between DLL3 expression and overall survival time in days (DSS). (A) Forest plot of DSS associations in 34 types of tumor. (B) Kaplan-Meier analysis of the association between DLL3 expression and DSS.

Figure 4

Association between DLL3 expression and overall survival time in days (DFI). (A) Forest plot of DFI associations in 34 types of tumor. (B) Kaplan-Meier analysis of the association between DLL3 expression and DFI.

Figure 5

Association between DLL3 expression and overall survival time in days (PFI). (A) Forest plot of PFI associations in 34 types of tumor. (B) Kaplan-Meier analysis of the association between DLL3 expression and PFI.

Figure 6

The correlation coefficients between DLL3 expression and the tumor microenvironment. Correlation between DLL3 and the immune, stromal, and tumor purity scores in 34 types of cancer.

Figure 7

Relationship between DLL3 expression and tumor infiltration of different immune cells.

Figure 8

Co-expression of DLL3 and immune-related genes. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 9

Associations between DLL3 expression and tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR). (A) Radar plot illustrating the relationship between DLL3 and TMB. (B) Radar plot illustrating the relationship between DLL3 and MSI. (C) Heatmap illustrating the association between DLL3 expression and MMR genes. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 10

Results of GSVA. Bubble plot show the 15 pathways of Hallmark (A) and KEGG (B) with the most significant positive and negative, respectively.