Department of Neurosurgery, Peking University Third Hospital, Beijing, China.
Center for Precision Neurosurgery and Oncology of Peking University Health Science Center, Beijing, China.
World Neurosurg. 2022 Sep;165:e650-e663. doi: 10.1016/j.wneu.2022.06.124. Epub 2022 Jun 30.
Previous studies have demonstrated the role of S100A10 in the progression of several tumors; however, few studies have investigated its immunological characteristics in adult gliomas. In this study, we systematically explored its biological features and clinical significance in adult gliomas.
Altogether, 325 glioma cases from the Chinese Glioma Genome Atlas and 699 glioma cases from The Cancer Genome Atlas were included as the training and validation cohorts. R software was used for data analysis and mapping using the RNA sequencing data from these cases. One-way analysis of variance and Student's t-test were used to assess the differences between the groups. Differences were considered statistically significant at P < 0.05.
We found that S100A10 was remarkably highly expressed in high-grade glioma, isocitrate dehydrogenase wild type, 1p19q noncodeletion type, O-methylguanine-DNA methyltransferase promoter unmethylation type, and mesenchymal-like molecular subtype. S100A10 specifically and sensitively indicates the mesenchymal-like molecular subtype. Upregulated S100A10 levels were independently correlated with poor survival. S100A10-related biological processes in gliomas mainly concentrate on immunoreaction and inflammatory response. We then proved that S100A10 was positively related to most inflammatory metagenes, except IgG, including HCK, LCK, MHC II, STAT1, and interferon. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of S100A10, especially in tumor-related macrophages, regulatory T cells, and myeloid-derived suppressor cells.
S100A10 is closely related to malignant pathological subtypes, worse prognosis, and immunosuppressive immune cell infiltration in adult gliomas, making it a promising biomarker and potential target in the diagnosis, treatment, and prognostic assessment of gliomas.
先前的研究表明 S100A10 在几种肿瘤的进展中起作用；然而，很少有研究调查其在成人胶质瘤中的免疫学特征。在这项研究中，我们系统地探讨了其在成人胶质瘤中的生物学特征和临床意义。
共纳入中国胶质瘤基因组图谱的 325 例胶质瘤病例和癌症基因组图谱的 699 例胶质瘤病例作为训练和验证队列。使用 R 软件对这些病例的 RNA 测序数据进行数据分析和映射。使用方差分析和学生 t 检验评估组间差异。P<0.05 时差异有统计学意义。
我们发现 S100A10 在高级别胶质瘤、异柠檬酸脱氢酶野生型、1p19q 非缺失型、O-甲基鸟嘌呤-DNA 甲基转移酶启动子未甲基化型和间充质样分子亚型中表达显著升高。S100A10 特异性和敏感地指示间充质样分子亚型。上调的 S100A10 水平与不良生存独立相关。胶质瘤中与 S100A10 相关的生物学过程主要集中在免疫反应和炎症反应上。我们随后证明 S100A10 与大多数炎症相关基因呈正相关，除 IgG 外，包括 HCK、LCK、MHC II、STAT1 和干扰素。更重要的是，肿瘤浸润免疫细胞的水平与 S100A10 的表达呈正相关，尤其是在肿瘤相关巨噬细胞、调节性 T 细胞和髓源性抑制细胞中。
S100A10 与成人胶质瘤中恶性病理亚型、预后不良和免疫抑制性免疫细胞浸润密切相关，使其成为胶质瘤诊断、治疗和预后评估中很有前途的生物标志物和潜在靶点。
