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PSAT1 作为骨髓增生异常综合征 (MDS) 治疗靶点的新见解。

New insights into PSAT1 as a therapeutic target for myelodysplastic syndrome (MDS).

机构信息

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.

出版信息

PLoS One. 2024 Aug 26;19(8):e0309456. doi: 10.1371/journal.pone.0309456. eCollection 2024.

DOI:10.1371/journal.pone.0309456
PMID:39186541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11346733/
Abstract

The metabolomic landscape in myelodysplastic syndrome (MDS) is highly deregulated and presents promising avenues for understanding disease pathogenesis and potential molecular dependencies. Here, we evaluated the transcriptomic landscape in MDS in multiple independent studies focusing more on metabolomics pathways. Identifying molecular dependencies will pave the way for a more precise disease stratification as well as the development of novel personalized treatment strategies. The study adopted a retrospective, cross-sectional approach, utilizing transcriptomic data from multiple MDS studies. The transcriptomic data were then subjected to comprehensive analyses, including differential gene expression, gene enrichment analysis, gene co-expression analysis, protein-protein interaction analyses, and survival analyses. PSAT1 showed a significant upregulation profile in MDS patients. This observed upregulation is correlated with the deregulation of immune-related pathways in MDS samples. This observation suggests a novel role for PSAT1 in immune modulation and potentially in augmenting immune evasion, which may lead to poor prognosis. This was evident in other tumors in the TCGA database, where cancer patients with high PSAT1 expression have a shorter overall survival. This study unveils a novel potential therapeutic avenue in MDS. Identifying the role of the PSAT1 gene sheds light on the disease's intricate biology, highlighting the ongoing cross-talk between metabolism and immune regulation, which may pave the way for innovative treatment modalities.

摘要

骨髓增生异常综合征 (MDS) 的代谢组学景观高度失调,为了解疾病发病机制和潜在的分子依赖性提供了有前景的途径。在这里,我们在多个独立研究中评估了 MDS 的转录组景观,更侧重于代谢组学途径。确定分子依赖性将为更精确的疾病分层以及新的个性化治疗策略的发展铺平道路。该研究采用回顾性、横断面方法,利用来自多个 MDS 研究的转录组数据。然后对转录组数据进行了全面分析,包括差异基因表达、基因富集分析、基因共表达分析、蛋白质-蛋白质相互作用分析和生存分析。PSAT1 在 MDS 患者中表现出显著的上调谱。这种观察到的上调与 MDS 样本中免疫相关途径的失调相关。这一观察结果表明 PSAT1 在免疫调节中具有新的作用,并且可能增强免疫逃逸,从而导致预后不良。在 TCGA 数据库中的其他肿瘤中也可以看到这种情况,在这些肿瘤中,高 PSAT1 表达的癌症患者总生存期更短。这项研究揭示了 MDS 中的一个新的潜在治疗途径。确定 PSAT1 基因的作用揭示了该疾病复杂的生物学,强调了代谢和免疫调节之间的持续相互作用,这可能为创新的治疗方式铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d29/11346733/277d3083cd35/pone.0309456.g007.jpg
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本文引用的文献

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PSAT1 enhances the efficacy of the prognosis estimation nomogram model in stage-based clear cell renal cell carcinoma.PSAT1 增强了基于分期的透明细胞肾细胞癌预后评估列线图模型的疗效。
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Overexpression of PSAT1 is Correlated with Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer.PSAT1 过表达与非小细胞肺癌的不良预后和免疫浸润相关。
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骨髓增生异常综合征的流行病学和发病机制。
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Downregulation of PSAT1 inhibits cell proliferation and migration in uterine corpus endometrial carcinoma.下调 PSAT1 抑制子宫体子宫内膜癌中的细胞增殖和迁移。
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Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant.靶向 PSAT1 以减轻 p53-72Pro 变体肿瘤的转移。
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