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lncRNA 特征通过调控宫颈癌肿瘤免疫微环境介导线粒体通透性转换驱动的细胞坏死。

lncRNA signature mediates mitochondrial permeability transition-driven necrosis in regulating the tumor immune microenvironment of cervical cancer.

机构信息

Department of Biomedical Engineering, Nanchang Hang Kong University, Nanchang, 330063, Jiangxi, China.

Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China.

出版信息

Sci Rep. 2024 Jul 29;14(1):17406. doi: 10.1038/s41598-024-65990-6.


DOI:10.1038/s41598-024-65990-6
PMID:39075098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11286791/
Abstract

Mitochondrial permeability transition (MPT)-driven necrosis (MPTDN) was a regulated variant of cell death triggered by specific stimuli. It played a crucial role in the development of organisms and the pathogenesis of diseases, and may provide new strategies for treating various diseases. However, there was limited research on the mechanisms of MPTDN in cervical cancer (CESC) at present. In this study, Weighted Gene Co-expression Network Analysis (WGCNA) was performed on differentially expressed genes in CESC. The module MEyellow, which showed the highest correlation with the phenotype, was selected for in-depth analysis. It was found that the genes in the MEyellow module may be associated with the tumor immune microenvironment (TIME). Through COX univariate regression and LASSO regression analysis, 6 key genes were identified. These genes were further investigated from multiple perspectives, including their independent diagnostic value, prognostic value, specific regulatory mechanisms in the tumor immune microenvironment, drug sensitivity analysis, and somatic mutation analysis. This study provided a comprehensive exploration of the mechanisms of action of these 6 key genes in CESC patients. And qRT-PCR validation was also conducted. Through COX univariate regression and LASSO coefficient screening of the MEyellow module, 6 key genes were identified: CHRM3-AS2, AC096734.1, BISPR, LINC02446, LINC00944, and DGUOK-AS1. Evaluation of the independent diagnostic value of these 6 key genes revealed that they can serve as independent diagnostic biomarkers. Through correlation analysis among these 6 genes, a potential regulatory mechanism among them was identified. Therefore, a risk prognostic model was established based on the collective action of these 6 genes, and the model showed good performance in predicting the survival period of CESC patients. By studying the relationship between these 6 key genes and the tumor microenvironment of CESC patients from multiple angles, it was found that these 6 genes are key regulatory factors in the tumor immune microenvironment of CESC patients. Additionally, 16 drugs that are associated with these 6 key genes were identified, and 8 small molecule drugs were predicted based on the lncRNA-mRNA network. The 6 key genes can serve as independent biomarkers for diagnosis, and the Risk score of these genes when acting together can be used as an indicator for predicting the clinical survival period of CESC patients. Additionally, these 6 key genes were closely related to the tumor immune microenvironment of CESC patients and were the important regulatory factors in the tumor immune microenvironment of CESC patients.

摘要

线粒体通透性转换(MPT)驱动的坏死(MPTDN)是一种受特定刺激触发的细胞死亡的调节变体。它在生物发育和疾病发病机制中起着关键作用,并可能为治疗各种疾病提供新的策略。然而,目前对于宫颈癌(CESC)中 MPTDN 的机制研究有限。在本研究中,对 CESC 中的差异表达基因进行了加权基因共表达网络分析(WGCNA)。选择与表型相关性最高的模块 MEyellow 进行深入分析。结果发现,MEyellow 模块中的基因可能与肿瘤免疫微环境(TIME)有关。通过 COX 单因素回归和 LASSO 回归分析,鉴定出 6 个关键基因。从多个角度进一步研究这些基因,包括它们在肿瘤免疫微环境中的独立诊断价值、预后价值、特定调控机制、药物敏感性分析和体细胞突变分析。本研究对这些关键基因在 CESC 患者中的作用机制进行了全面探讨。并进行了 qRT-PCR 验证。通过 MEyellow 模块的 COX 单因素回归和 LASSO 系数筛选,鉴定出 6 个关键基因:CHRM3-AS2、AC096734.1、BISPR、LINC02446、LINC00944 和 DGUOK-AS1。这些关键基因的独立诊断价值评估表明,它们可以作为独立的诊断生物标志物。通过对这 6 个基因的相关性分析,发现了它们之间潜在的调控机制。因此,基于这 6 个基因的集体作用,建立了一个风险预后模型,该模型在预测 CESC 患者的生存期方面表现良好。通过从多个角度研究这 6 个关键基因与 CESC 患者肿瘤微环境的关系,发现这 6 个基因是 CESC 患者肿瘤免疫微环境的关键调节因子。此外,还鉴定出与这 6 个关键基因相关的 16 种药物,并基于 lncRNA-mRNA 网络预测了 8 种小分子药物。这 6 个关键基因可以作为独立的诊断生物标志物,这些基因共同作用的风险评分可作为预测 CESC 患者临床生存期的指标。此外,这 6 个关键基因与 CESC 患者的肿瘤免疫微环境密切相关,是 CESC 患者肿瘤免疫微环境的重要调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/d88531d3f75f/41598_2024_65990_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6fb299f8f617/41598_2024_65990_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6109ca887e28/41598_2024_65990_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/32eebd342338/41598_2024_65990_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/fd7fcc11191e/41598_2024_65990_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/ad7203033481/41598_2024_65990_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6eeb3c22a3bc/41598_2024_65990_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/2531a9e255b6/41598_2024_65990_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/eeda340595d9/41598_2024_65990_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/3f4666e58ea8/41598_2024_65990_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/dced8e03f953/41598_2024_65990_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/d88531d3f75f/41598_2024_65990_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6fb299f8f617/41598_2024_65990_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6109ca887e28/41598_2024_65990_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/b6c9158040d8/41598_2024_65990_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/32eebd342338/41598_2024_65990_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/024465bcede5/41598_2024_65990_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/fd7fcc11191e/41598_2024_65990_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/ad7203033481/41598_2024_65990_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/6eeb3c22a3bc/41598_2024_65990_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/2531a9e255b6/41598_2024_65990_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/eeda340595d9/41598_2024_65990_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/3f4666e58ea8/41598_2024_65990_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/dced8e03f953/41598_2024_65990_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57de/11286791/d88531d3f75f/41598_2024_65990_Fig13_HTML.jpg

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引用本文的文献

[1]
The construction and evaluation of a prognostic risk score model for HCC based on MPT-related lncRNAs.

Front Oncol. 2025-7-28

[2]
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Discov Oncol. 2025-6-13

[3]
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[4]
Identification and multi-dimensional validation of mitochondrial permeability transition-driven necrosis-related model to assess the prognosis and immunotherapy value in breast cancer.

Eur J Med Res. 2025-2-18

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