Abstract
BackgroundThe activation of succinate receptor 1 (SUCNR1) by extracellular succinate has been found to regulate immune cell function. However, the clinical significance of SUCNR1 in ovarian cancer and its correlation with tumor-infiltrating lymphocytes remain unclear.MethodsThe genetic alteration and expression patterns of SUCNR1 were analyzed by using cBioPortal and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier Plotter was used to assess the prognostic value of SUCNR1 in patients with ovarian cancer. The correlations between SUCNR1 expression and immune infiltration, gene markers of immune cells, cytokines, chemokines, or T cell exhaustion were explored by using TIMER and TISIDB platforms. We also performed Gene Set Enrichment Analysis (GSEA) to reveal biological function of SUCNR1 in ovarian cancer.ResultsThe expression of SUCNR1 was closely related to tumor infiltrating lymphocytes, multiple gene markers of immune cells, and T cell exhaustion in ovarian cancer. The expression of SUCNR1 was also associated with the expression of cytokine- or chemokine-related genes. Moreover, GSEA revealed that various immune-related pathways might be regulated by SUCNR1. In addition, we found that SUCNR1 was amplified in ovarian cancer, and the high expression of SUCNR1 predicted worse progression-free survival (p = 0.0073, HR = 1.49, 95% CI = 1.11–2).ConclusionThese results highlight the role of SUCNR1 in regulating tumor immunity in ovarian cancer.
Highlights
Accumulating evidences indicate that tumor microenvironment (TME) and immune cell infiltration play critical roles in the development and treatment of cancers (Anandappa et al, 2020; Galon and Bruni, 2020)
To explore whether succinate-related regulators were involved in the infiltration of immune cells in ovarian cancer, we first investigated the association between nine succinate-related regulators with molecular subtypes of ovarian cancer by using the TISIDB platform
We demonstrated that the expression of succinate receptor 1 (SUCNR1) was significantly associated with the abundance of immune cells, such as activated CD8+ T cells, effector memory CD8+ T cells, activated CD4+ T cells, effector memory CD4+ T cells, regulatory T cells, natural killer cells, neutrophils, macrophages, activated dendritic cells, activated B cells, and myeloid-derived suppressor cells (MDSC), in ovarian cancer (Figure 1C)
Summary
Accumulating evidences indicate that tumor microenvironment (TME) and immune cell infiltration play critical roles in the development and treatment of cancers (Anandappa et al, 2020; Galon and Bruni, 2020). As an important intermediate of the tricarboxylic acid cycle, succinate can induce inflammatory cytokines (IL1β, IL-6, IL-8, and TNF-α) (Tannahill et al, 2013; Park et al, 2018; Li et al, 2019a) It has been demonstrated as a signal for the process involved in various pathological statuses, such as ischemia, hypoxia, metabolic disorders, and cancers (Tretter et al, 2016; Jiang and Yan, 2017; Kula-Alwar et al, 2019). The clinical significance of SUCNR1 in ovarian cancer and its correlation with tumor-infiltrating lymphocytes remain unclear
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