CD38 Predicts Favorable Prognosis by Enhancing the Immune Infiltration and Antitumor Immunity in Epithelial Ovarian Cancer Microenvironment

Abstract

Background: Identifying predictive biomarker and novel target to optimize the immunotherapy strategies for epithelial ovarian cancer (EOC) is urgent needed. CD38 is a multifunctional glycoprotein that acts as ectoenzyme and immune receptor. However, the underlying immunological mechanisms and prognostic value of CD38 in EOC is remain unclear. Methods: CD38 gene expression in EOC was evaluated in Gene Expression Profiling Interactive Analysis (GEPIA) and TISIDB database. The prognostic value was calculated using GEPIA and Kaplan-Meier plotter. And Gene Set Enrichment Analysis was conducted to study the roles of CD38 in EOC microenvironment. Furthermore, the relationship between CD38 expression level and immune cells infiltration were analyzed by Tumor Immune Estimation Resource (TIMER) and TISIDB. Results: The GEPIA and TISIDB database shown that CD38 expression in EOC was higher than normal tissue and expressed highest in immunoreactive subtype among four molecular types. 424 cases from GEPIA revealed that high levels of CD38 was associated with longer disease-free survival (HR=0.66, P=0.00089) and increased overall survival (HR=0.67, P=0.0016), Kaplan-Meier plotter also confirms the prognostic value of CD38 in EOC. Data from TCGA database demonstrated that gene signatures in many categories, such as immune response and adaptive immune response, were enriched in EOC samples with CD38 highly expression. Besides, CD38 was positively correlated with immune cells infiltrating, especially activated CD8+ T cells, CD4+ T cells and B cells. Conclusions: CD38 is positively correlated with prognosis and immune cells infiltrating in EOC microenvironment, and contributes to regulation of antitumor immunity. CD38 could be used as a prognostic biomarker and potentially immunotherapy target. Funding Statement: This study was supported in part through the Natural Science Foundation of Zhejiang Province (LY17H160028, ZGZ). Declaration of Interests: The authors stated: No potential conflicts of interest were disclosed. Ethics Approval Statement: Not required.