Abstract
Historically, immunotherapies have only resulted in a partial response from patients with advanced ovarian cancer, resulting in poor clinical efficacy. A full understanding of immune-related gene expression and immunocyte infiltration in ovarian cancer would be instrumental for the improved implementation of immunotherapy. The Capping Actin Protein, Gelsolin-Like (CAPG) gene encodes an actin-regulatory protein, which plays important roles in tumor progression and immune regulation. This study is aimed at identifying the potential therapeutic and prognostic roles of CAPG in ovarian cancer. CAPG expression and clinical information were investigated in the data collected from TCGA, Oncomine, GEPIA, UALCAN, and Kaplan-Meier plotter. CAPG coexpression networks were evaluated by LinkedOmics, GeneMANIA, and NetworkAnalyst. The correlation of CAPG with immune infiltrates was analyzed via TIMER, ImmuCellAI, and GEPIA. Our result showed that patients with high tumoral CAPG expression had significantly shorter 5-year overall survival. Functional enrichment analysis indicated that CAPG-related phenotypes were largely involved in inflammatory response, chemokine and cytokine signaling, cell adhesion, and Toll-like receptor signaling pathways. CAPG expression was positively correlated with infiltrating levels of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and exhausted T cells (Texs) while being negatively correlated with infiltrating levels of natural killer T cells (NKTs) and neutrophils in ovarian cancer. Moreover, the expression of FOXP3, CD25, CD127, CCR8, and TGFβ in respect to Tregs; CCL2 and CD68 in respect to TAM; CD163, VSIG4, and MS4A4A in respect to M2 macrophages; CD33 and CD11b in respect to myeloid-derived suppressor cells (MDSCs); and PD1, CTLA4, LAG3, TIM3, GZMB, 2B4, and TIGIT in respect to Texs was significantly correlated with CAPG expression in ovarian cancer. These findings suggest that CAPG may contribute to the immunosuppressive tumor microenvironment in ovarian cancer, leading to an exhausted T cell phenotype and tumor progression. Therefore, CAPG can be used as a potential biomarker for determining prognosis and immunotherapy effectiveness in ovarian cancer.
Highlights
Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide [1]
The results showed that CAPG expression was higher in numerous solid tumors when compared to the normal tissues most notably in brain cancer, breast cancer, ovarian cancer, and pancreatic cancer (Figure 1(a))
We examined CAPG expression across multiple malignancies in the Gene Expression Profiling Interactive Analysis (GEPIA) database and found that CAPG levels were significantly higher in BRCA, GBM, OV, and PAAD when compared to adjacent normal tissues (Figure 1(b))
Summary
Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide [1]. Most patients are not diagnosed until they reach advanced stages, contributing to a 5-year overall survival (OS) rate of less than 30% [2]. Most of stage III–IV patients that have an initial complete response to surgery and chemotherapy will experience disease progression and resistance to the first-line treatment regimen [4]. The primary adjuvant treatment for ovarian cancer has advanced from chemotherapy to targeted molecular therapy [5]. Immunotherapies, such as vaccination, adoptive cellular therapy, and checkpoint inhibitors, have become an attractive therapeutic strategy [6]. Immune checkpoint blockade (ICB) therapies such as cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed death-1/ligand (PD-1/PD-L1) inhibitors showed promising antitumor effects in many cancers, they only exhibited a Disease Markers partial response and poor clinical efficacy in advanced OC [7, 8]. In order to improve the efficacy of immunotherapies for OC, there is an urgent need for a more comprehensive understanding of immune-related gene expression and immunocyte infiltration in respect to the disease
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