Comprehensive analysis reveals cholesterol metabolism-related signature for predicting prognosis and guiding individualized treatment of glioma.

IF 3.6 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Heliyon Pub Date : 2025-01-02 eCollection Date: 2025-01-15 DOI:10.1016/j.heliyon.2024.e41601

Dengfeng Lu, Fei Wang, Yayi Yang, Aojie Duan, Yubo Ren, Yun Feng, Haiying Teng, Zhouqing Chen, Xiaoou Sun, Zhong Wang

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Abstract

Objective: Gliomas are the most common intracranial tumors with the highest degree of malignancy. Disturbed cholesterol metabolism is one of the key features of many malignant tumors, including gliomas. This study aimed to investigate the significance of cholesterol metabolism-related genes in prognostic prediction and in guiding individualized treatment of patients with gliomas.

Methods: Transcriptional data and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Intraoperative glioma samples retained in our unit and the corresponding clinicopathological information were also collected with the patients' knowledge. Firstly, cholesterol metabolism-related gene signatures (CMRGS) were identified and constructed based on difference analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and univariate/multivariate COX analysis. Then, the role of CMRGS in predicting the prognosis of gliomas and distinguishing immune landscapes was evaluated by using nomograms, survival analysis, enrichment analysis, and immune-infiltration analysis. Finally, the drug sensitivity of gliomas in different risk groups was evaluated using the oncoPredict algorithm, and potentially sensitive chemotherapeutic and molecular-targeted drugs were identified.

Results: The prognostic CMRGS contained seven genes: APOE, SCD, CXCL16, FABP5, S100A11, TNFRSF12A, and ELOVL2. Patients were divided into high- and low-risk groups based on the median cholesterol metabolic index (CMI). There were significant differences in clinicopathological characteristics and overall survival between groups. COX analysis suggested that CMRGS was an independent risk factor for glioma prognosis and had a better predictive performance than several classical indicators. In addition, GSEA, immune infiltration analysis showed that CMRGS could differentiate the immune landscapes of patients in groups. The reliability of CMRGS was validated in the CGGA cohort and our Gusu cohort. Finally, 14 drugs sensitive to high-risk patients and 16 drugs sensitive to low-risk patients were identified.

Conclusion: The CMRGS reliably predicts glioma prognosis in multiple cohorts and may be useful in guiding individualized treatment.

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综合分析发现，胆固醇代谢相关特征可预测预后，指导胶质瘤的个体化治疗。

目的：胶质瘤是颅内最常见的恶性程度最高的肿瘤。胆固醇代谢紊乱是包括胶质瘤在内的许多恶性肿瘤的主要特征之一。本研究旨在探讨胆固醇代谢相关基因在胶质瘤患者预后预测和指导个体化治疗中的意义。方法：从肿瘤基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库中获取转录数据和临床病理数据。术中保留在我单位的胶质瘤标本和相应的临床病理资料也在患者知情的情况下收集。首先，基于差异分析、最小绝对收缩和选择算子（LASSO）回归分析和单因素/多因素COX分析，对胆固醇代谢相关基因特征（CMRGS）进行识别和构建。然后，通过形态学分析、生存分析、富集分析和免疫浸润分析，评估CMRGS在预测胶质瘤预后和区分免疫景观中的作用。最后，使用oncoppredict算法评估不同风险组胶质瘤的药物敏感性，并确定潜在敏感的化疗药物和分子靶向药物。结果：预后CMRGS包含7个基因：APOE、SCD、CXCL16、FABP5、S100A11、TNFRSF12A和ELOVL2。根据中位胆固醇代谢指数（CMI）将患者分为高危组和低危组。两组患者的临床病理特征及总生存率差异有统计学意义。COX分析提示CMRGS是胶质瘤预后的独立危险因素，其预测效果优于几种经典指标。此外，GSEA、免疫浸润分析显示，CMRGS可以区分各组患者的免疫景观。CMRGS的可靠性在CGGA队列和我们的Gusu队列中得到了验证。最终确定高危患者敏感的药物14种，低危患者敏感的药物16种。结论：CMRGS能可靠地预测胶质瘤的预后，可用于指导个体化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Heliyon MULTIDISCIPLINARY SCIENCES-

CiteScore

4.50

自引率

2.50%

发文量

2793

期刊介绍： Heliyon is an all-science, open access journal that is part of the Cell Press family. Any paper reporting scientifically accurate and valuable research, which adheres to accepted ethical and scientific publishing standards, will be considered for publication. Our growing team of dedicated section editors, along with our in-house team, handle your paper and manage the publication process end-to-end, giving your research the editorial support it deserves.