SPP1 is associated with glioma malignancy and immunosuppressive regulation in 916 samples

Glioma is a disease typically characterized by immunosuppression, which explains its poor prognosis. Therefore, it is urgent to elucidate new molecular mechanisms of immune-supervised escape to improve the efficacy of immunotherapy. Recent studies have identified secreted phosphoprotein 1(SPP1) as a pro-inflammatory and chemokine in macrophages that mediates crosstalk between the innate immune system and tumor cells. We aimed to detect the role of SPP1 in immunomodulation in glioma. We enrolled 916 patients from different ethnic groups, including 603 patients from The Cancer Genome Atlas (TCGA) database and 313 patients from the Chinese Glioma Genome Atlas (CGGA) database. We performed enrichment analysis and used GSVA to calculate the immune pathway and immune cell infiltration scores of SPP1.In addition, we investigated the correlation between SPP1 and immune checkpoint genes as well as inflammation-related genes. The expression of SPP1 is significantly elevated in IDH wild-type gliomas and high-grade gliomas, particularly in the mesenchymal subtype, and it serves as an independent prognostic factor for overall survival (OS) in glioma patients. SPP1 influences macrophage activation, cytokine secretion, and polarization and exhibits a strong association with various lymphocytes, including T, B and NK cells. Furthermore, SPP1 is strongly correlated not only with immune checkpoint genes but also with various inflammation-related genes. In conclusion, SPP1 expression is tightly linked to the molecular pathology of gliomas and is highly correlated with immune checkpoints. It contributes to glioma immune evasion, positioning SPP1 as a promising new target for immunotherapy in glioma.

胶质瘤(Glioma)是一类以免疫抑制为典型特征的疾病，这也是其预后不佳的重要原因。因此，阐明肿瘤免疫逃逸的新型分子机制以提升免疫治疗疗效已成为当前亟待解决的问题。既往研究证实，分泌型磷蛋白1(secreted phosphoprotein 1, SPP1)是巨噬细胞中的促炎趋化因子，可介导先天免疫与肿瘤细胞间的串扰。本研究旨在探究SPP1在胶质瘤免疫调节中的作用。本研究纳入了来自不同种族的916例患者，其中包括癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库中的603例患者，以及中国胶质瘤基因组图谱(Chinese Glioma Genome Atlas, CGGA)数据库中的313例患者。我们开展了富集分析，并利用基因集变异分析(Gene Set Variation Analysis, GSVA)计算SPP1相关的免疫通路及免疫细胞浸润评分。此外，我们还分析了SPP1与免疫检查点基因及炎症相关基因的相关性。研究结果显示，SPP1在异柠檬酸脱氢酶野生型(IDH wild-type)胶质瘤及高级别胶质瘤中表达显著升高，尤其在间质亚型中最为显著；同时，SPP1可作为胶质瘤患者总生存期(Overall Survival, OS)的独立预后因素。SPP1可影响巨噬细胞活化、细胞因子分泌及极化过程，并与T细胞、B细胞、NK细胞等多种淋巴细胞存在强相关性。此外，SPP1不仅与免疫检查点基因密切相关，还与多种炎症相关基因存在显著关联。综上，SPP1的表达与胶质瘤的分子病理特征紧密相关，且与免疫检查点存在高度相关性；其可促进胶质瘤的免疫逃逸，有望成为胶质瘤免疫治疗的新型潜在靶点。