| 摘要: |
| 目的 借助癌症基因组图谱（TCGA）数据库研究低级别胶质瘤（LGG）组织中补体C3a受体1（C3AR1）的表达水平及其与LGG患者预后及肿瘤免疫细胞浸润的关系。方法 从TCGA数据库下载514例LGG患者的基因表达谱数据和临床信息。比较C3AR1基因在LGG组织和正常组织中的表达水平，分析不同WHO分级LGG组织样本中C3AR1基因的表达量及与患者预后的关系，分析LGG患者临床特征和C3AR1基因表达水平对患者预后的影响，分析LGG组织中C3AR1基因表达与肿瘤免疫细胞浸润的相关性及免疫细胞浸润水平对患者预后的影响。对与C3AR1基因表达呈正相关的基因群进行京都基因与基因组百科全书（KEGG）通路富集分析。结果 LGG组织中C3AR1基因表达水平高于正常组织（P<0.05）。C3AR1基因在WHOⅢ级LGG组织中的表达高于WHOⅡ级（P<0.05），C3AR1基因低表达组患者的预后优于高表达组（HR=1.7，95% CI 1.1～2.4，P=0.003 6)。患者年龄、LGG级别和C3AR1基因表达水平是LGG的独立预后因素（P均<0.01）。C3AR1基因的表达水平与LGG的免疫细胞浸润水平呈正相关（P均<0.01），且后者影响LGG患者预后。与C3AR1基因表达呈正相关基因群的干扰素γ介导的信号通路、Ig/主要组织相容性复合体（MHC）保守位点、Ig样Cl型结构域、MHC Ⅰ/Ⅱ类抗原识别蛋白、连接肽特定区域、Toll样受体信号通路等多条通路参与调控LGG。结论 C3AR1与LGG的预后和免疫细胞浸润有关，可能成为LGG分级诊断、免疫治疗和预后判断的生物标志物。 |
| 关键词: 补体C3a受体1 低级别胶质瘤 预后 肿瘤免疫细胞浸润 肿瘤生物标记 |
| DOI：10.16781/j.0258-879x.2021.05.0495 |
| 投稿时间：2020-07-11修订日期：2020-11-12 |
| 基金项目: |
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| Association of complement C3a receptor 1 with low-grade glioma prognosis and immune cell infiltration |
| ZHU Kai-xin△,ZHANG Ye-lei△,HOU Xiao-xiang,QU Xiao-lin,ZHANG Dan-feng,WANG Shen-hao,HOU Li-jun* |
(Department of Neurosurgery, Changzheng Hospital, Naval Medical University(Second Military Medical University), Shanghai 200003, China
△Co-first authors.
* Corresponding author) |
| Abstract: |
| Objective To analyze the expression of complement C3a receptor 1 (C3AR1) in low-grade glioma (LGG) tissues and the association with the prognosis and immune cell infiltration in LGG based on The Cancer Genome Atlas (TCGA) database. Methods The gene expression profile data and clinical information of 514 LGG patients were downloaded from TCGA database. The expression levels of C3AR1 in LGG and normal tissues were compared. The expression levels of C3AR1 in different World Health Organization (WHO) grades of LGG tissues and their relationship with prognosis were analyzed. The influence of clinical features and C3AR1 expression level on prognosis of LGG patients was analyzed. The correlation between C3AR1 expression in LGG tissues and tumor immune cell infiltration, and the influence of immune cell infiltration level on prognosis were analyzed, and gene groups positively correlated with the expression of C3AR1 were further analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Results The expression of C3AR1 in LGG tissues was significantly higher than that in normal tissues (P<0.05). The expression of C3AR1 was higher in WHO gradeⅢ LGG tissues than in WHO gradeⅡ tissues (P<0.05). The prognosis of C3AR1 low-expression group was significantly better than that of the high-expression group (hazard ratio=1.7, 95% confidence interval 1.1-2.4, P=0.003 6). Patient age, LGG grade and expression level of C3AR1 were independent prognostic factors of LGG (all P<0.01). The expression level of C3AR1 was positively correlated with the immune cell infiltration level of LGG (all P<0.01), and the latter was related to the prognosis of LGG patients. Gene groups positively related to C3AR1 regulated several LGG-related key pathways:interferon γ-mediated signaling pathway, conserved immunoglobulin (Ig)/major histocompatibility complex (MHC) site, Ig-like Cl type domains, MHC class Ⅰ/Ⅱ-like antigen recognition protein, specific regions of junctional peptide, and Toll-like receptor signaling pathways. Conclusion C3AR1 is associated with the prognosis and immune cell infiltration of LGG, and it can be a biomarker for grading diagnosis, immunotherapy and prognosis of LGG. |
| Key words: complement C3a receptor 1 low-grade glioma prognosis tumor immune cell infiltration tumor biomarkers |
