Zhu Ying, Zhang Zhigang, Jiang Zhou, Liu Yang, Zhou Jianwei
Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China.
Front Genet. 2020 Apr 30;11:369. doi: 10.3389/fgene.2020.00369. eCollection 2020.
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, = 0.00089] and increased overall survival rate ( = 0.67, = 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.
迫切需要鉴定预测性生物标志物和新靶点，以优化上皮性卵巢癌（EOC）的免疫治疗策略。CD38是一种多功能糖蛋白，作为一种胞外酶和免疫受体发挥作用。然而，CD38在EOC中的潜在免疫机制和预后价值仍不清楚。通过使用基因表达谱交互分析（GEPIA）和TISIDB数据库评估EOC中CD38基因的表达。使用GEPIA和Kaplan-Meier绘图仪计算预后价值。进行基因集富集分析以研究CD38在EOC微环境中的作用。此外，通过肿瘤免疫估计资源和TISIDB分析CD38表达水平与免疫细胞浸润之间的关系。GEPIA和TISIDB数据库显示，EOC中CD38的表达高于正常组织，并且在四种分子类型中的免疫反应亚型中最高。GEPIA的424例病例显示，高水平的CD38与更长的无病生存期相关[风险比（HR）=0.66，P = 0.00089]，总生存率增加（P = 0.67，P = 0.0016）。Kaplan-Meier绘图仪也证实了CD38在EOC中的预后价值。来自癌症基因组图谱数据库的数据表明，许多类别中的基因特征，如免疫反应和适应性免疫反应，在高CD38表达的EOC样本中富集。此外，CD38与免疫细胞浸润呈正相关，尤其是活化的CD8 T细胞、CD4 T细胞和B细胞的浸润。CD38与EOC微环境中的预后和免疫细胞浸润呈正相关，并有助于抗肿瘤免疫的调节。CD38可作为预后生物标志物和潜在的免疫治疗靶点。
