Data Sheet 2_A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients.csv

IntroductionGrade II/III gliomas are invasive brain tumors with a high risk of malignant progression and significant clinical heterogeneity, highlighting the urgent need for reliable prognostic biomarkers to guide personalized treatment strategies. This study aimed to investigate the molecular mechanisms driving glioma progression and to identify potential therapeutic targets.
MethodsWe analyzed 200 mitochondrial oxidative phosphorylation (OXPHOS)-related genes in 512 grade II/III glioma samples from The Cancer Genome Atlas (TCGA). Consensus clustering identified two distinct molecular subtypes (C1 and C2). Differentially expressed genes (DEGs) between subtypes were determined using the limma package. The immune cell composition and tumor microenvironment (TME) characteristics were assessed using ESTIMATE, MCPcounter, and CIBERSORT algorithms. Based on prognostic DEGs, we constructed a four-gene prognostic signature (MAOB, IGFBP2, SERPINA1, and LGR6).
ResultsThe C2 molecular subtype was associated with poorer prognosis, higher immune scores, and enrichment in tumor-promoting pathways. The four-gene signature demonstrated strong prognostic performance and robustness across multiple independent validation cohorts. Immunohistochemical (IHC) analysis of clinical glioma specimens confirmed elevated protein expression levels of the four genes in tumor tissues.
DiscussionOur OXPHOS-associated gene signature provides novel insights into the molecular classification, immune landscape, and prognosis of grade II/III gliomas. These findings lay the foundation for precision oncology and the development of targeted therapeutic interventions.

引言
II/III级胶质瘤是一类侵袭性脑肿瘤，具有较高的恶性进展风险与显著的临床异质性，亟需可靠的预后生物标志物以指导个体化治疗策略。本研究旨在探究驱动胶质瘤进展的分子机制，并筛选潜在治疗靶点。

方法
我们对来自癌症基因组图谱（The Cancer Genome Atlas, TCGA）的512例II/III级胶质瘤样本中的200个线粒体氧化磷酸化（mitochondrial oxidative phosphorylation, OXPHOS）相关基因开展了分析。通过一致性聚类鉴定出两种截然不同的分子亚型（C1与C2）。采用limma包鉴定亚型间的差异表达基因（differentially expressed genes, DEGs）。利用ESTIMATE、MCPcounter及CIBERSORT算法评估了免疫细胞组成及肿瘤微环境（tumor microenvironment, TME）特征。基于预后相关DEGs，我们构建了包含MAOB、IGFBP2、SERPINA1及LGR6的四基因预后特征。

结果
C2分子亚型与更差的预后、更高的免疫评分及肿瘤促进通路富集显著相关。该四基因预后特征在多个独立验证队列中均表现出优异的预后预测性能与稳定性。对临床胶质瘤标本开展的免疫组化（immunohistochemical, IHC）分析证实，肿瘤组织中这四个基因的蛋白表达水平显著升高。

讨论
本研究构建的OXPHOS相关基因特征为II/III级胶质瘤的分子分型、免疫图谱及预后评估提供了全新视角。这些研究结果为精准肿瘤学及靶向治疗干预手段的开发奠定了坚实基础。