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整合多组学分析揭示了与线粒体相关的转录组特征与低级别脑胶质瘤肿瘤免疫微环境之间的联系。

Integrative multi-omics analysis unveils the connection between transcriptomic characteristics associated with mitochondria and the tumor immune microenvironment in lower-grade gliomas.

机构信息

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.

出版信息

Sci Rep. 2024 Oct 10;14(1):23675. doi: 10.1038/s41598-024-74281-z.

DOI:10.1038/s41598-024-74281-z
PMID:39390013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11467307/
Abstract

Lower-grade gliomas (LGGs) exhibit diverse clinical behaviors and varying immune infiltration levels. Mitochondria have been implicated in numerous cancer pathogenesis and development, including LGGs. However, the precise biological functions of mitochondrial genes in shaping the immune landscape and the prognostic significance of LGGs remain elusive. Utilizing the Mito-Carta3.0 database, we curated a total of 1136 genes implicated in mitochondrial functions. By leveraging the expression profiles of 1136 genes related to mitochondria, we successfully categorized LGGs into four distinctive mitochondria-related transcriptome (MRT) subtypes. Our thorough analysis conclusively demonstrated that these subtypes exhibited marked disparities. To enable a personalized and integrated evaluation of LGG patients, we developed a prognostic signature known as MRT-related prognostic signature (MTRS). MTRS demonstrated correlation with mitochondria-related transcriptome (MRT) subtypes, allowing the assessment of patients' prognosis and immune microenvironment. We conducted a detailed exploration of the single-cell distribution of MTRS in lower-grade gliomas and verified the core genes of MTRS within the spatial transcriptome of these tumors. Furthermore, our study pinpointed MGME1 as the pivotal gene in the model, functioning as an oncogene that exerts influence on cell proliferation and migration capabilities. Our research highlights the importance of mitochondrial transcriptomic features in LGGs, offering paths for tailored therapies.

摘要

低级别胶质瘤（LGG）表现出不同的临床行为和不同的免疫浸润水平。线粒体参与了许多癌症的发病机制和发展，包括 LGG。然而，线粒体基因在塑造免疫景观中的精确生物学功能以及 LGG 的预后意义仍不清楚。利用 Mito-Carta3.0 数据库，我们整理了总共 1136 个与线粒体功能相关的基因。通过利用与线粒体相关的 1136 个基因的表达谱，我们成功地将 LGG 分为四个不同的与线粒体相关的转录组（MRT）亚型。我们的全面分析明确表明，这些亚型表现出明显的差异。为了实现对 LGG 患者的个性化和综合评估，我们开发了一种称为与线粒体相关的预后签名（MTRS）的预后签名。MTRS 与与线粒体相关的转录组（MRT）亚型相关，可评估患者的预后和免疫微环境。我们详细探讨了 MTRS 在低级别胶质瘤中的单细胞分布，并在这些肿瘤的空间转录组中验证了 MTRS 的核心基因。此外，我们的研究确定了 MGME1 作为模型中的关键基因，作为一种影响细胞增殖和迁移能力的癌基因。我们的研究强调了线粒体转录组特征在 LGG 中的重要性，为靶向治疗提供了途径。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/8de362e3cc05/41598_2024_74281_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/5f3342ae7b24/41598_2024_74281_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/c2ddbb363f11/41598_2024_74281_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/cad752c9e344/41598_2024_74281_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/d96f26bcfe16/41598_2024_74281_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/cc36b74cb226/41598_2024_74281_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b089/11467307/ba8fbcdeec47/41598_2024_74281_Fig12_HTML.jpg

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