全面分析胆固醇代谢在低级别胶质瘤中的临床和生物学意义。
Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas.
机构信息
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
出版信息
BMC Cancer. 2023 Jul 24;23(1):692. doi: 10.1186/s12885-023-10897-0.
BACKGROUND
As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs).
METHODS
The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature.
RESULTS
Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients.
CONCLUSION
The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs.
背景
作为膜脂质的组成部分和氧化固醇和类固醇激素的前体，重新编程的胆固醇代谢有助于多种癌症的发生和发展。因此，我们旨在进一步研究胆固醇代谢在低级别胶质瘤（LGG）中的意义。
方法
本研究纳入了来自 TCGA RNA-seq 数据集的 413 例 LGG 样本（训练队列）和来自 CGGA RNA-seq 数据集的 172 例 LGG 样本（验证队列）。采用 LASSO 回归模型确定胆固醇代谢相关特征。进行生物信息学分析以探讨该特征在 LGG 中的功能作用。采用 Kaplan-Meier 分析和 Cox 回归分析评估风险特征的预后价值。
结果
我们的研究结果表明，胆固醇代谢与 LGG 的临床病理特征和基因组改变密切相关。生物信息学分析表明，胆固醇代谢在 LGG 的免疫抑制中起关键作用，主要通过促进巨噬细胞极化和 T 细胞耗竭。Kaplan-Meier 曲线和 Cox 回归分析表明，胆固醇代谢是 LGG 患者的独立预后指标。为了提高风险特征的临床应用价值，我们还构建了列线图模型来预测 LGG 患者的 1 年、3 年和 5 年生存率。
结论
胆固醇代谢是一个强大的预后指标，可以作为增强 LGG 个体化治疗的有前途的靶点。
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