Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and Institutes of Brain Science, Fudan University, Shanghai, 200040, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of General Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.
Comput Biol Med. 2024 May;174:108457. doi: 10.1016/j.compbiomed.2024.108457. Epub 2024 Apr 8.
Glioma is a common malignant brain tumor with great heterogeneity and huge difference in clinical outcomes. Although lymphotoxin (LT) beta receptor (LTBR) has been linked to immune system and response development for decades, the expression and function in glioma have not been investigated. To confirm the expression profile of LTBR, integrated RNA-seq data from glioma and normal brain tissues were analyzed. Functional enrichment analysis, TMEscore analysis, immune infiltration, the correlation of LTBR with immune checkpoints and ferroptosis, and scRNAseq data analysis in gliomas were in turn performed, which pointed out that LTBR was pertinent to immune functions of macrophages in gliomas. In addition, after being trained and validated in the tissue samples of the integrated dataset, an LTBR DNA methylation-based prediction model succeeded to distinguish gliomas from non-gliomas, as well as the grades of glioma. Moreover, by virtue of the candidate LTBR CpG sites, a prognostic risk-score model was finally constructed to guide the chemotherapy, radiotherapy, and immunotherapy for glioma patients. Taken together, LTBR is closely correlated with immune functions in gliomas, and LTBR DNA methylation could serve as a biomarker for diagnosis and prognosis of gliomas.
神经胶质瘤是一种常见的恶性脑肿瘤,具有很大的异质性和临床结局的巨大差异。尽管淋巴毒素 (LT)β 受体 (LTBR) 数十年来一直与免疫系统和反应的发展有关,但它在神经胶质瘤中的表达和功能尚未得到研究。为了证实 LTBR 的表达谱,分析了神经胶质瘤和正常脑组织的综合 RNA-seq 数据。依次进行了功能富集分析、TMEscore 分析、免疫浸润、LTBR 与免疫检查点和铁死亡的相关性以及神经胶质瘤的 scRNAseq 数据分析,这些结果表明 LTBR 与神经胶质瘤中巨噬细胞的免疫功能有关。此外,在综合数据集的组织样本中经过训练和验证后,基于 LTBR 甲基化的预测模型成功地区分了神经胶质瘤与非神经胶质瘤,以及神经胶质瘤的分级。此外,通过候选的 LTBR CpG 位点,最终构建了一个预后风险评分模型,以指导神经胶质瘤患者的化疗、放疗和免疫治疗。总之,LTBR 与神经胶质瘤中的免疫功能密切相关,LTBR 甲基化可以作为神经胶质瘤诊断和预后的生物标志物。