Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
CNS Neurosci Ther. 2022 Jan;28(1):158-171. doi: 10.1111/cns.13749. Epub 2021 Oct 25.
Growth differentiation factor 15 (GDF15) is involved in lots of crucial inflammatory and immune response. The clinical and immune features for GDF15 in glioma have not been specifically investigated so far.
Gene expression profiles obtained from public glioma datasets were used to explore the biological function of GDF15 and its impact on immune microenvironment. Interference with GDF15 in several glioma cell lines to verify its functions in vitro. Survival data were used for the survival analysis and establishment of a nomogram predictive model.
GDF15 was up-regulated in various malignant phenotypes of glioma. Function analysis and in vitro experiments revealed that GDF15 was associated with malignant progression and NF-κB pathway. GDF15 was closely correlated to inflammatory response, infiltrating immune cells, and immune checkpoint molecules, especially in lower grade glioma (LGG). High expression level of GDF15 predicted poor survival in LGG, while the effect on glioblastoma (GBM) was not significant. A nomogram predictive model combining GDF15 and other prognostic factors was constructed and showed ideal predictive performance.
GDF15 could serve as an interesting prognostic biomarker for LGG. Regulating the expression of GDF15 may help solve the dilemma of immunotherapy in glioma.
生长分化因子 15(GDF15)参与了许多关键的炎症和免疫反应。迄今为止,尚未专门研究 GDF15 在神经胶质瘤中的临床和免疫特征。
使用来自公共神经胶质瘤数据集的基因表达谱来探讨 GDF15 的生物学功能及其对免疫微环境的影响。在几种神经胶质瘤细胞系中干扰 GDF15,以验证其在体外的功能。生存数据用于生存分析和建立列线图预测模型。
GDF15 在各种恶性神经胶质瘤表型中上调。功能分析和体外实验表明,GDF15 与恶性进展和 NF-κB 途径有关。GDF15 与炎症反应、浸润免疫细胞和免疫检查点分子密切相关,尤其是在低级别神经胶质瘤(LGG)中。GDF15 高表达预示着 LGG 的生存不良,而对胶质母细胞瘤(GBM)的影响不显著。构建了一个结合 GDF15 和其他预后因素的列线图预测模型,显示出理想的预测性能。
GDF15 可以作为 LGG 的一个有趣的预后生物标志物。调节 GDF15 的表达可能有助于解决神经胶质瘤免疫治疗的困境。