预后标记物C3AR1与卵巢癌细胞在肿瘤微环境中的增殖和免疫抑制有关。
Prognostic marker C3AR1 is associated with ovarian cancer cell proliferation and immunosuppression in the tumor microenvironment.
发表日期:2023 Apr 01
作者:
Jinfa Huang, Lei Zhou, Kaixian Deng
来源:
Journal of Ovarian Research
摘要:
C3AR1被报道在多种癌症中驱动肿瘤免疫力。然而,它在卵巢癌中的作用还不清楚。本研究旨在确定C3AR1在卵巢癌(OC)的预后和调节肿瘤浸润免疫细胞中的作用。C3AR1的表达、预后以及临床相关数据从公共数据库如TCGA、HPA和CPTAC中收集,并进一步分析它们与免疫渗透的关系。免疫组化验证了C3AR1在卵巢癌和对照组织中的表达。C3AR1经质粒转染在SKOV3细胞中被迫表达,并通过qRT-PCR和Western blot进行验证。细胞增殖的评估通过EdU试验进行。TCGA、CPTAC的生物信息学分析和临床样本的免疫组化染色确认高C3AR1在卵巢癌中的表达比正常组织高。高C3AR1表达预示着不良的临床结局。KEGG和GO分析显示C3AR1在卵巢癌中的生物过程主要涉及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如CCR1(R=0.83)、IL10RA(R=0.92)和INFG(R=0.74)呈正相关。此外,增加C3AR1表达预测更多的肿瘤相关巨噬细胞、树突状细胞和CD8+T细胞浸润。一些重要的m6A调节因子如IGF2BP2、ALKBH5、IGFBP3和METL14与C3AR1存在显著的正或负相关。最后,C3AR1的过表达显著增加了SKOV3细胞的增殖。总之,我们的研究表明C3AR1与卵巢癌的预后和免疫细胞渗透有关,并且是一个有前途的免疫治疗目标。©2023.作者。
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).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.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.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.© 2023. The Author(s).