Abstract
The identification of predictive biomarkers and novel targets to optimize immunotherapy strategies for epithelial ovarian cancer (EOC) is urgently needed. CD38 is a multifunctional glycoprotein that acts as an ectoenzyme and immune receptor. However, the underlying immunological mechanisms and prognostic value of CD38 in EOC remain unclear. CD38 gene expression in EOC was evaluated by using Gene Expression Profiling Interactive Analysis (GEPIA) and TISIDB database. The prognostic value was calculated using GEPIA and Kaplan–Meier plotter. Gene set enrichment analysis was conducted to study the roles of CD38 in the EOC microenvironment. Furthermore, the relationship between CD38 expression level and immune cell infiltration was analyzed by the Tumor Immune Estimation Resource and TISIDB. The GEPIA and TISIDB databases showed that CD38 expression in EOC was higher than that in normal tissue and was highest in the immunoreactive subtype among the four molecular types. A total of 424 cases from GEPIA revealed that high levels of CD38 were associated with longer disease-free survival [hazard ratio (HR) = 0.66, P = 0.00089] and increased overall survival rate (HR = 0.67, P = 0.0016). Kaplan–Meier plotter also confirmed the prognostic value of CD38 in EOC. Data from The Cancer Genome Atlas database demonstrated that gene signatures in many categories, such as immune response and adaptive immune response, were enriched in EOC samples with high CD38 expression. In addition, CD38 was positively correlated with immune cell infiltration, especially infiltration of activated CD8+ T cells, CD4+ T cells, and B cells. CD38 is positively correlated with prognosis and immune cell infiltration in the EOC microenvironment and contributes to the regulation of antitumor immunity. CD38 could be used as a prognostic biomarker and potential immunotherapy target.
Highlights
Epithelial ovarian cancer (EOC) is the seventh most common cancer and seriously threatens female health worldwide (Siegel et al, 2019)
Survival analysis of CD38 in EOC was performed by using Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA), and these two databases used the log-rank test for hypothesis evaluation
The results showed that the CD38 expression level in EOC was higher than that in normal ovarian tissue (Figure 1A)
Summary
Epithelial ovarian cancer (EOC) is the seventh most common cancer and seriously threatens female health worldwide (Siegel et al, 2019). Studies have demonstrated that CD38 is involved in CD8+ T-cell suppression via adenosine receptor signaling in the TME, which can cause resistance to PD-1/PD-L1 blockade therapy (Chen et al, 2018). These results showed that CD38 plays multifaceted functional roles in lymphocytes and in the TME. CD38 was correlated with tumor-infiltrating lymphocytes (TILs), especially with activated CD8+ T cells These findings uncover the important immunoregulatory role of CD38 in the EOC microenvironment and provide a potential target for ovarian cancer immunotherapy
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