研究动态
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将临床和空间数据整合以探索脂质代谢相关基因,以预测胶质瘤的预后和免疫微环境。

Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and immune microenvironment in gliomas.

发表日期:2023 Mar 16
作者: Zhangyi Yu, Yuneng Zhou, Yongxue Li, Zhiqiang Dong
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

脂质代谢对于胶质瘤的生长、免疫微环境和药物敏感性至关重要。识别胶质瘤的预后指标和阐明其进展机制对于改善患者预后至关重要。在本研究中,我们通过对来自GEO、CGGA和TCGA的数据集进行综合分析,探讨了代谢相关基因在胶质瘤中的作用和预后价值。基于临床数据和转录组数据,我们发现与更好的预后和免疫浸润有关的三条与脂质代谢相关的主要通路的表达模式为高脂肪酸、高磷脂、低甘油三酯。涉及这三条通路的基因被用于生成一个预后模型,该模型在测试集和验证集中表现出高稳定性和高效性。胶质瘤患者的空间转录组揭示了具有高风险基因CAV1和SCD的表达区域的微环境处于缺氧、上皮-间充质转化和细胞周期阻滞状态,因此可以用作肿瘤微环境中代谢重编程的标记。在高风险组中,M0巨噬细胞和M1巨噬细胞显著富集,风险评分与风险基因的基因突变和甲基化显著相关。我们进一步进行了相应于不同风险基因的药物敏感性筛选。本研究为不同代谢相关基因表达模式的差异免疫微环境提供了新的见解,并强调了肿瘤进展和代谢重编程的时空协同性。©2023年。作者(们)独家许可给德国施普林格出版公司,施普林格自然出版集团的一部分。
Lipid metabolism is crucial to tumor growth and immune microenvironment as well as drug sensitivity in glioma. Identifying prognostic indicators of glioma and elucidating the mechanisms of glioma progression are critical for improving the prognosis of glioma patients. In this study, we investigated the role and prognostic value of metabolism-related genes in glioma by integrative analysis of datasets from GEO, CGGA, and TCGA. Based on clinical data and transcriptome data, we found that the expression pattern of three major pathways related to lipid metabolism is fatty acidhigh-phospholipidhigh-triglyceridelow, which is associated with better prognosis and immune infiltration. The genes involved in these three pathways were used to generate a prognostic model, which showed high stability and efficiency in the test set and validation set. The spatial transcriptome of glioma patients revealed that the microenvironment of the regions with high expression of risk genes CAV1 and SCD is in a state of hypoxia, EMT, and cell cycle arrest, and thus can be used as markers of metabolic reprogramming in the tumor microenvironment. In the high-risk group, M0 macrophages and M1 macrophages were significantly enriched, and the risk score was significantly correlated with gene mutation and methylation of risk genes. We further performed drug sensitivity screening corresponding to different risk genes. This study provided novel insights into the differential immune microenvironment with different expression patterns of metablism-related genes and highlighted the spatial and temporal synergy of tumor progression and metabolic reprogramming.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.