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使用线粒体相关基因对膀胱癌患者进行新型诊断模型的机器学习预测。

Machine-learning prediction of a novel diagnostic model using mitochondria-related genes for patients with bladder cancer.

作者信息

Li Jian, Wang Zhiyong, Wang Tianen

机构信息

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Sci Rep. 2024 Apr 23;14(1):9282. doi: 10.1038/s41598-024-60068-9.

Abstract

Bladder cancer (BC) is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Mitochondrial Dysfunction is involved in the progression of BC. This study aimed to developed a novel diagnostic model based on mitochondria-related genes (MRGs) for BC patients using Machine Learning. In this study, we analyzed GSE13507 datasets and identified 752 DE-MRGs in BC specimens. Functional enrichment analysis uncovered the significant roles of 752 DE-MRGs in key processes such as cellular and organ development, as well as gene regulation. The analysis revealed the crucial functions of these genes in transcriptional regulation and protein-DNA interactions. Then, we performed LASSO and SVM-RFE, and identified four critical diagnostic genes including GLRX2, NMT1, OXSM and TRAF3IP3. Based on the above four genes, we developed a novel diagnostic model whose diagnostic value was confirmed in GSE13507, GSE3167 and GSE37816 datasets. Moreover, we reported the expressing pattern of GLRX2, NMT1, OXSM and TRAF3IP3 in BC samples. Immune cell infiltration analysis revealed that the four genes were associated with several immune cells. Finally, we performed RT-PCR and confirmed NMT1 was highly expressed in BC cells. Functional experiments revealed that knockdown of NMT1 suppressed the proliferation of BC cells. Overall, we have formulated a diagnostic potential that offered a comprehensive framework for delving into the underlying mechanisms of BC. Before proceeding with clinical implementation, it is essential to undertake further investigative efforts to validate its diagnostic effectiveness in BC patients.

摘要

膀胱癌(BC)是全球第九大常见癌症,其发病率和死亡率都很高。线粒体功能障碍与膀胱癌的进展有关。本研究旨在利用机器学习为膀胱癌患者开发一种基于线粒体相关基因(MRGs)的新型诊断模型。在本研究中,我们分析了GSE13507数据集,并在膀胱癌标本中鉴定出752个差异表达的线粒体相关基因。功能富集分析揭示了752个差异表达的线粒体相关基因在细胞和器官发育以及基因调控等关键过程中的重要作用。分析还揭示了这些基因在转录调控和蛋白质-DNA相互作用中的关键功能。然后,我们进行了LASSO和支持向量机递归特征消除(SVM-RFE),并鉴定出四个关键诊断基因,包括谷胱甘肽还原酶2(GLRX2)、N-乙酰转移酶1(NMT1)、氧化应激诱导跨膜蛋白(OXSM)和肿瘤坏死因子受体相关因子3相互作用蛋白3(TRAF3IP3)。基于上述四个基因,我们开发了一种新型诊断模型,其诊断价值在GSE13507、GSE3167和GSE37S16数据集中得到了证实。此外,我们报告了GLRX2、NMT1、OXSM和TRAF3IP3在膀胱癌样本中的表达模式。免疫细胞浸润分析表明,这四个基因与几种免疫细胞有关。最后,我们进行了逆转录-聚合酶链反应(RT-PCR),并证实NMT1在膀胱癌细胞中高表达。功能实验表明,敲低NMT1可抑制膀胱癌细胞的增殖。总体而言,我们制定了一种具有诊断潜力的方法,为深入研究膀胱癌的潜在机制提供了一个全面的框架。在进行临床应用之前,必须进一步开展研究工作,以验证其对膀胱癌患者的诊断有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5360/11039685/bf546b2d4bdb/41598_2024_60068_Fig1_HTML.jpg

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