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基于机器学习的鉴定与胶质瘤预后和免疫浸润相关的细胞死亡特征。

Machine learning-based identification of a cell death-related signature associated with prognosis and immune infiltration in glioma.

机构信息

The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

出版信息

J Cell Mol Med. 2024 Jun;28(11):e18463. doi: 10.1111/jcmm.18463.

Abstract

Accumulating evidence suggests that a wide variety of cell deaths are deeply involved in cancer immunity. However, their roles in glioma have not been explored. We employed a logistic regression model with the shrinkage regularization operator (LASSO) Cox combined with seven machine learning algorithms to analyse the patterns of cell death (including cuproptosis, ferroptosis, pyroptosis, apoptosis and necrosis) in The Cancer Genome Atlas (TCGA) cohort. The performance of the nomogram was assessed through the use of receiver operating characteristic (ROC) curves and calibration curves. Cell-type identification was estimated by using the cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and single sample gene set enrichment analysis methods. Hub genes associated with the prognostic model were screened through machine learning techniques. The expression pattern and clinical significance of MYD88 were investigated via immunohistochemistry (IHC). The cell death score represents an independent prognostic factor for poor outcomes in glioma patients and has a distinctly superior accuracy to that of 10 published signatures. The nomogram performed well in predicting outcomes according to time-dependent ROC and calibration plots. In addition, a high-risk score was significantly related to high expression of immune checkpoint molecules and dense infiltration of protumor cells, these findings were associated with a cell death-based prognostic model. Upregulated MYD88 expression was associated with malignant phenotypes and undesirable prognoses according to the IHC. Furthermore, high MYD88 expression was associated with poor clinical outcomes and was positively related to CD163, PD-L1 and vimentin expression in the in-horse cohort. The cell death score provides a precise stratification and immune status for glioma. MYD88 was found to be an outstanding representative that might play an important role in glioma.

摘要

越来越多的证据表明,多种细胞死亡方式广泛参与了癌症免疫。然而,它们在神经胶质瘤中的作用尚未被探索。我们采用带有收缩正则算子(LASSO)Cox 的逻辑回归模型与七种机器学习算法,分析了癌症基因组图谱(TCGA)队列中细胞死亡(包括铜死亡、铁死亡、细胞焦亡、细胞凋亡和细胞坏死)的模式。通过使用接受者操作特征(ROC)曲线和校准曲线来评估列线图的性能。通过使用细胞类型鉴定相对已知 RNA 转录本子集(CIBERSORT)和单样本基因集富集分析方法来估计细胞类型鉴定。通过机器学习技术筛选与预后模型相关的枢纽基因。通过免疫组织化学(IHC)来研究 MYD88 的表达模式和临床意义。细胞死亡评分是神经胶质瘤患者预后不良的独立预后因素,其准确性明显优于 10 个已发表的特征。列线图在根据时间依赖性 ROC 和校准图预测结局方面表现良好。此外,高风险评分与免疫检查点分子的高表达和促肿瘤细胞的密集浸润显著相关,这些发现与基于细胞死亡的预后模型有关。IHC 结果显示,上调的 MYD88 表达与恶性表型和不良预后相关。此外,在内部队列中,高 MYD88 表达与不良临床结局相关,并且与 CD163、PD-L1 和波形蛋白的表达呈正相关。细胞死亡评分可以为神经胶质瘤提供精确的分层和免疫状态。MYD88 是一个出色的代表性基因,可能在神经胶质瘤中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c66/11157676/380271eda526/JCMM-28-e18463-g006.jpg

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