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蛋白磷酸酶表达对肝细胞癌患者预后的影响

Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.

作者信息

Mestareehi Aktham, Abu-Farsakh Noor

机构信息

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Isra University, P.O. Box 22, Amman 11622, Jordan.

Department of Pharmaceutical Sciences, School of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, United States.

出版信息

ACS Omega. 2024 Feb 20;9(9):10299-10331. doi: 10.1021/acsomega.3c07787. eCollection 2024 Mar 5.

Abstract

The study was conducted to unveil the significance of protein phosphatases in the prognosis of hepatocellular carcinoma (HCC) patients and its related molecular biological attributes as well as to discover novel potential biomarkers for therapeutic significance and diagnostic purposes that may benefit clinical practice. Analyzing a data set from 159 HCC patients using high-throughput phosphoproteomics, we examined the dysregulated expression of protein phosphatases. Employing bioinformatic and pathway analyses, we explored differentially expressed genes linked to protein phosphatases. A protein-protein interaction network was constructed using the search tool for the retrieval of interacting genes/proteins database. We quantified a total of 11,547 phosphorylation sites associated with 4043 phosphoproteins from HCC patients. Within this data set, we identified 105 identified phosphorylation sites associated with protein phosphatases; 28 genes were upregulated and 3 were downregulated in HCC. Enriched pathways using Gene Set Enrichment Analysis encompassed oocyte meiosis, proteoglycans in cancer, the oxytocin signaling pathway, the cGMP-PKG signaling pathway, the vascular smooth muscle, and the cAMP signaling pathway. The Kyoto encyclopedia of genes and genomes (KEGG) analysis highlighted pathways like mitogen-activated protein kinase, AMPK, and PI3K-Akt, indicating potential involvement in HCC progression. Notably, the PPI network identified hub genes, emphasizing their interconnections and potential roles in HCC. In our study, we found significantly upregulated levels of CDC25C, PPP1R13L, and PPP1CA, which emerge as promising avenues. This significant expression could serve as potent diagnostic and prognostic markers to enhance the effectiveness of HCC cancer treatment, offering efficiency and accuracy in patient assessment. The findings regarding protein phosphatases reveal their elevated expression in HCC, correlating with unfavorable prognosis. Moreover, the outcomes of gene ontology and KEGG pathway analyses suggest that protein phosphatases may influence liver cancer by engaging diverse targets and pathways, ultimately fostering the progression of HCC. These results underscore the substantial potential of protein phosphatases as key contributors to HCC's development and advancement. This insight holds promise for identifying therapeutic targets and charting research avenues to enhance the comprehension of the intricate molecular mechanisms underpinning HCC.

摘要

本研究旨在揭示蛋白磷酸酶在肝细胞癌(HCC)患者预后中的意义及其相关分子生物学特性,并发现具有治疗意义和诊断价值的新型潜在生物标志物,以造福临床实践。通过高通量磷酸化蛋白质组学分析159例HCC患者的数据集,我们检测了蛋白磷酸酶的表达失调情况。利用生物信息学和通路分析,我们探索了与蛋白磷酸酶相关的差异表达基因。使用检索相互作用基因/蛋白质数据库的搜索工具构建了蛋白质-蛋白质相互作用网络。我们对来自HCC患者的4043种磷酸化蛋白质共11547个磷酸化位点进行了定量分析。在该数据集中,我们鉴定出105个与蛋白磷酸酶相关的磷酸化位点;HCC中有28个基因上调,3个基因下调。使用基因集富集分析(Gene Set Enrichment Analysis)富集的通路包括卵母细胞减数分裂、癌症中的蛋白聚糖、催产素信号通路、cGMP-PKG信号通路、血管平滑肌和cAMP信号通路。京都基因与基因组百科全书(KEGG)分析突出了丝裂原活化蛋白激酶、AMPK和PI3K-Akt等通路,表明它们可能参与HCC进展。值得注意的是,蛋白质-蛋白质相互作用网络确定了枢纽基因,强调了它们在HCC中的相互联系和潜在作用。在我们的研究中,我们发现CDC25C、PPP1R13L和PPP1CA的水平显著上调,这成为有前景的研究方向。这种显著表达可作为有效的诊断和预后标志物,以提高HCC癌症治疗的有效性,在患者评估中提供效率和准确性。关于蛋白磷酸酶的研究结果表明它们在HCC中表达升高,与不良预后相关。此外,基因本体论和KEGG通路分析的结果表明,蛋白磷酸酶可能通过参与多种靶点和通路影响肝癌发生,最终促进HCC的进展。这些结果强调了蛋白磷酸酶作为HCC发展和进展的关键因素的巨大潜力。这一见解有望识别治疗靶点并规划研究途径,以加深对HCC复杂分子机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5252/10918787/8ccdfa2791c2/ao3c07787_0001.jpg

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