Huang Ruoyu, Li Guanzhang, Wang Kuanyu, Wang Zhiliang, Zeng Fan, Hu Huimin, Jiang Tao
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Cell Dev Biol. 2021 Jul 9;9:619396. doi: 10.3389/fcell.2021.619396. eCollection 2021.
As a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.
A total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment were performed to explore the biological implication of this signature.
We found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.
The ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.
内质网作为蛋白质和脂质合成的关键细胞器，其功能障碍对细胞的多种生物学过程有重大影响。因此，在本研究中，我们构建了一种内质网应激相关风险特征，以研究内质网应激在胶质瘤中的功能作用。
本研究纳入了来自TCGA RNA测序数据集的626个样本（训练队列）和来自CGGA RNA测序数据集的310个样本（验证队列）。还获取了临床信息和基因组概况。通过LASSO回归模型建立内质网应激特征。通过Cox回归、Kaplan-Meier和ROC曲线分析评估风险特征的预后价值。进行生物信息学分析和实验以探索该特征的生物学意义。
我们发现内质网应激相关特征与胶质瘤的主要临床病理特征和基因组改变密切相关。Kaplan-Meier曲线和Cox回归分析表明，内质网应激激活是胶质瘤患者的独立预后因素。此外，我们还通过列线图和ROC曲线分析构建了个体化预后预测模型。生物信息学分析表明，内质网应激激活还促进了胶质瘤的恶性进展，并参与了肿瘤免疫微环境的调节，尤其是M2期巨噬细胞的浸润。这些结果在免疫组化分析和细胞生物学实验中得到进一步验证。
内质网应激激活具有较高的预后价值，可作为开发胶质瘤个体化治疗的有前景的靶点。
