Henan and Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, 475004, China.
Henan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, 475004, China.
Med Oncol. 2022 Jan 11;39(2):27. doi: 10.1007/s12032-022-01647-6.
Low-grade gliomas is the malignant nervous tumor with distinct biological and clinical characteristics. Despite advances in diagnostic and therapeutic methods, how to significantly elongate the survival of low-grade gliomas is still challengeable. Complement 3, as the critical component in the innate immune system, plays an essential role in local immune response and participating into regulation of the epithelial-mesenchymal transition and tumor microenvironment. In this study, we systematically determined the expression levels and immunological roles of C3 in low-grade gliomas using various public databases. Then, we further identified the impact of C3 expression on immune cell infiltration compared to normal tissue, indicating the effect of cellular microenvironment on overall survival of LGG patients. We obtained clinical characteristics, transcriptome, and survival of C3 in LGG from the TCGA, GEPIA2.0, and cBioportal databases. Two differentially expressed genes (DEGs) were obtained, DEGs compared to normal tissue (DEG_G1) and DEGs between C3 high expression and C3 low expression in LGG patients (DEG_G2). By performing the GO analysis and protein-protein interaction (PPI) network of DEG_G1, we have identified the top-ranked 10 hub genes, which are highly associated with regulation of cell cycle. The gene set enrichment analysis demonstrated that overexpression of C3 in LGG patient is positively correlated with regulation of cell cycle. The relative PPI analysis and GSEA of DEG_G2 were performed and analysis results indicated that higher expression of C3 in the LGG can activate immune-related pathways. Finally, immune cell infiltration analysis of C3 in the LGG patients was employed and clearly indicated that higher neutrophil infiltration can worsen the survival of the LGG patients with higher expression of C3. These results were confirmed by the Human Protein Atlas database, in which expression level of C3 protein in gliomas patients always higher. This investigation implied that C3 can be as diagnostic biomarker and potential targets of precise therapy for the LGG patients.
低级别神经胶质瘤是一种具有显著生物学和临床特征的恶性神经肿瘤。尽管在诊断和治疗方法方面取得了进展，但如何显著延长低级别神经胶质瘤患者的生存期仍然是一个挑战。补体 3 作为固有免疫系统的关键组成部分，在局部免疫反应中发挥着重要作用，并参与调节上皮-间充质转化和肿瘤微环境。在这项研究中，我们使用各种公共数据库系统地确定了 C3 在低级别神经胶质瘤中的表达水平和免疫学作用。然后，我们进一步确定了 C3 表达水平与正常组织相比对免疫细胞浸润的影响，表明细胞微环境对 LGG 患者总生存期的影响。我们从 TCGA、GEPIA2.0 和 cBioportal 数据库中获得了 LGG 中 C3 的临床特征、转录组和生存数据。我们获得了 LGG 中 C3 的差异表达基因（DEG）、与正常组织相比的差异表达基因（DEG_G1）和 LGG 患者中 C3 高表达与 C3 低表达之间的差异表达基因（DEG_G2）。通过对 DEG_G1 进行 GO 分析和蛋白质-蛋白质相互作用（PPI）网络分析，我们确定了排名前 10 的 hub 基因，这些基因与细胞周期调控高度相关。基因集富集分析表明，LGG 患者中 C3 的过表达与细胞周期调控呈正相关。对 DEG_G2 进行相对 PPI 分析和 GSEA 分析，结果表明，LGG 中 C3 的高表达可激活免疫相关途径。最后，我们对 LGG 患者中 C3 的免疫细胞浸润进行了分析，结果表明，C3 高表达患者中中性粒细胞浸润增加会使患者的生存状况恶化。人类蛋白质图谱数据库的结果证实了这一点，该数据库显示，胶质瘤患者的 C3 蛋白表达水平始终较高。这项研究表明，C3 可以作为 LGG 患者的诊断生物标志物和潜在的精准治疗靶点。
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