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泛素激活酶E1(UBA1)作为乳腺癌的预后生物标志物和治疗靶点:对免疫浸润及功能影响的见解

Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.

作者信息

Feng Mingtao, Cui Huanhuan, Li Sen, Li Liangdong, Zhou Changshuai, Chen Lei, Cao Yiqun, Gao Yang, Li Deheng

机构信息

Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

Int J Mol Sci. 2024 Nov 26;25(23):12696. doi: 10.3390/ijms252312696.

DOI:10.3390/ijms252312696
PMID:39684409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11641640/
Abstract

Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of was observed to be notably enhanced in cancer tissues relative to controls, and high expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS). Moreover, exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC.

摘要

泛素激活酶E1(UBA1)是一种参与泛素酶激活的E1酶,已被证实与人类多种癌症的发生和发展有关。然而,UBA1在乳腺癌(BC)中的具体作用仍不清楚。在本研究中,我们进行了深入调查,以阐明UBA1在BC中的意义并验证其功能。通过分析BC患者的mRNA测序数据,我们发现癌组织中UBA1的mRNA表达相对于对照组显著增强,并且高表达与较差的总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFS)相关。此外,UBA1有望成为BC患者独立的预后和诊断生物标志物。此外,功能富集分析显示UBA1参与炎症相关通路,如TNF-α信号通路、IL-6信号通路以及各种免疫相关生物学过程。值得注意的是,单样本基因集富集分析(ssGSEA)有助于确定UBA1表达与浸润性肥大细胞、Th1细胞、未成熟树突状细胞(iDC)、B细胞、树突状细胞(DC)、效应记忆T细胞(Tem)、细胞毒性细胞、T细胞、CD8+T细胞和浆细胞样树突状细胞(pDC)水平之间的负相关关系。最后,本研究表明沉默UBA1可显著抑制BC细胞系的生长和发育。这些发现突出了UBA1作为一种与BC免疫浸润相关的潜在预后生物标志物的作用,从而揭示了其作为BC患者新治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5299/11641640/4c6f4e8beab2/ijms-25-12696-g009.jpg
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