Department of Neurosurgery, Ningbo Medical Centre LiHuiLi Hospital, Ningbo, Zhejiang, China.
Medicine (Baltimore). 2024 May 10;103(19):e38091. doi: 10.1097/MD.0000000000038091.
To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG.
为了筛选低级别胶质瘤（LGG）中的免疫相关预后生物标志物，并揭示其潜在的调控机制。我们首先鉴定了存活患者和死亡患者之间的差异表达基因（DEGs），然后获得了 DEGs 和免疫相关基因之间的关键共同基因。对于与总生存期（OS）相关的关键 DEGs，我们通过 Kaplan-Meier、RCS、logistic 回归、ROC 和决策曲线分析方法评估了它们的临床价值。我们还评估了免疫浸润在关键 DEGs 与 OS 之间的相关性中的作用。所有分析均基于 TCGA-LGG 数据。最后，我们进行了分子对接分析，以探索关键 DEGs 与 LGG 治疗药物的靶向结合。在 146 个 DEGs 中，最终仅筛选出白细胞介素 6（IL-6）作为免疫相关生物标志物。IL-6 高表达与 OS 时间明显相关（均 P<.05），呈线性关系。IL-6 与 IDH1 突变的组合对生存状态具有最佳的预测性能，并且它们具有良好的临床净获益。接下来，我们发现 IL-6 与免疫微环境评分之间存在显著关系，并且免疫微环境在 IL-6 与生存之间的关联中起中介作用（均 P<.05）。详细地，IL-6 与 M1 巨噬细胞浸润丰度及其生物标志物呈正相关（均 P<.05）。最后，我们获得了 4 种针对 IL-6 的 LGG 治疗药物，并且验证了它们的靶向结合关系。IL6 作为一种免疫相关的生物标志物，与 LGG 的预后相关，并且可能成为 LGG 的治疗靶点。
