预后标志物 C3AR1 与卵巢癌细胞增殖及肿瘤微环境中的免疫抑制有关。

Prognostic marker C3AR1 is associated with ovarian cancer cell proliferation and immunosuppression in the tumor microenvironment.

机构信息

Department of Gynecology, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde), Foshan, 528308, Guangdong, China.

出版信息

J Ovarian Res. 2023 Apr 1;16(1):64. doi: 10.1186/s13048-023-01140-2.

DOI:10.1186/s13048-023-01140-2

PMID:37005667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10067206/

Abstract

BACKGROUND

C3AR1 was reported in driving tumor immunity in multiple cancers. However, its roles in ovarian cancer remain unclear. This study aims to determine role of C3AR1 in prognosis and regulating tumor infiltrating immune cells of ovarian cancer (OC).

MATERIALS AND METHODS

The expression, prognosis and clinical data related to C3AR1 were collected from public databases such as The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Clinical Proteomics Tumor Analysis Alliance (CPTAC), and further analyze their relationship with immune infiltration. Immunohistochemistry verified the expression of C3AR1 in ovarian cancer and control tissues. C3AR1 was forced expressed in SKOV3 cells by plasmid transfection, and verified by qRT-PCR and Western blot. Cell proliferation were evaluated by EdU assay.

RESULTS

Bioinformatics analysis (TCGA, CPTAC) and immunohistochemical staining of clinical samples confirmed higher C3AR1 expression in ovarian cancer than that in normal tissues. High C3AR1 expression predicted adverse clinical outcomes. KEGG and GO analysis showed that the biological processes of C3AR1 in ovarian cancer are mainly involved in T cell activation, cytokine and chemokine activation. C3AR1 expression was positively correlated with chemokines and their receptors in the tumor microenvironment, such as CCR1(R = 0.83), IL10RA (R = 0.92), and INFG (R = 0.74). In addition, increased C3AR1 expression predicted more infiltration of tumor-associated macrophages, dendritic cell and CD8 + T cell. Some important m6A regulators, such as IGF2BP2, ALKBH5, IGFBP3 and METL14, are significantly positively or negatively correlated with C3AR1. Finally, overexpression of C3AR1 significantly increased proliferation of SKOV3 cells.

CONCLUSION

In summary, our study suggested that C3AR1 is associated with the prognosis and immune cell infiltration of ovarian cancer, and is a promising immunotherapeutic target.

摘要

背景

C3AR1 已被报道在多种癌症中驱动肿瘤免疫。然而，其在卵巢癌中的作用尚不清楚。本研究旨在确定 C3AR1 在卵巢癌（OC）预后和调节肿瘤浸润免疫细胞中的作用。

材料和方法

从公共数据库（如癌症基因组图谱（TCGA）、人类蛋白质图谱（HPA）和临床蛋白质组肿瘤分析联盟（CPTAC））收集 C3AR1 的表达、预后和临床相关数据，并进一步分析其与免疫浸润的关系。免疫组织化学验证了 C3AR1 在卵巢癌和对照组织中的表达。通过质粒转染在 SKOV3 细胞中强制表达 C3AR1，并通过 qRT-PCR 和 Western blot 验证。通过 EdU 测定评估细胞增殖。

结果

生物信息学分析（TCGA、CPTAC）和临床样本的免疫组织化学染色证实，卵巢癌中 C3AR1 的表达高于正常组织。高 C3AR1 表达预示着不良的临床结局。KEGG 和 GO 分析表明，C3AR1 在卵巢癌中的生物学过程主要涉及 T 细胞激活、细胞因子和趋化因子激活。C3AR1 表达与肿瘤微环境中的趋化因子及其受体呈正相关，如 CCR1（R=0.83）、IL10RA（R=0.92）和 INFG（R=0.74）。此外，增加的 C3AR1 表达预示着肿瘤相关巨噬细胞、树突状细胞和 CD8+T 细胞的浸润增加。一些重要的 m6A 调节剂，如 IGF2BP2、ALKBH5、IGFBP3 和 METL14，与 C3AR1 呈显著正相关或负相关。最后，C3AR1 的过表达显著增加了 SKOV3 细胞的增殖。