Mou Jun, Zhang Min, Qin Fumin, Cui Yajie, Xu Keyou, Pang Baoye, Li Xinyue, Tan Wanyi, Yang Aiqi, Liu Yaxin, Shen Lingjun, Liu Yanting, Xu Kai
Laboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
Cancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
Front Immunol. 2025 Aug 1;16:1638824. doi: 10.3389/fimmu.2025.1638824. eCollection 2025.
Grade 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.
We 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).
The 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.
Our 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.
II/III级胶质瘤是侵袭性脑肿瘤，具有恶性进展的高风险和显著的临床异质性，这突出了对可靠预后生物标志物的迫切需求，以指导个性化治疗策略。本研究旨在探讨驱动胶质瘤进展的分子机制，并确定潜在的治疗靶点。
我们分析了来自癌症基因组图谱（TCGA）的512例II/III级胶质瘤样本中的200个线粒体氧化磷酸化（OXPHOS）相关基因。共识聚类确定了两种不同的分子亚型（C1和C2）。使用limma软件包确定亚型之间的差异表达基因（DEG）。使用ESTIMATE、MCPcounter和CIBERSORT算法评估免疫细胞组成和肿瘤微环境（TME）特征。基于预后DEG，我们构建了一个四基因预后特征（MAOB、IGFBP2、SERPINA1和LGR6）。
C2分子亚型与较差的预后、较高的免疫评分以及肿瘤促进途径的富集相关。四基因特征在多个独立验证队列中表现出强大的预后性能和稳健性。对临床胶质瘤标本的免疫组织化学（IHC）分析证实肿瘤组织中这四个基因的蛋白表达水平升高。
我们的OXPHOS相关基因特征为II/III级胶质瘤的分子分类、免疫格局和预后提供了新的见解。这些发现为精准肿瘤学和靶向治疗干预的发展奠定了基础。
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