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尤因肉瘤中一个新的泛素化相关基因的鉴定与验证

Identification and validation of a novel ubiquitination-related gene in Ewing's sarcoma.

作者信息

Qu Guoxin, Xu Yuanchun, Qu Ye, Qiu Jinchao, Chen Guosheng, Zhao Nannan, Deng Jin

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China.

Department of Emergency, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.

出版信息

Front Oncol. 2023 Feb 16;13:1000949. doi: 10.3389/fonc.2023.1000949. eCollection 2023.

DOI:10.3389/fonc.2023.1000949
PMID:36910645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9997212/
Abstract

BACKGROUND

Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods.

METHODS

The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression.

RESULTS

A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene () showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES.

CONLUSION

was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.

摘要

背景

尤因肉瘤(ES)是全球最常见的恶性骨肿瘤之一。然而,ES的基因和信号通路的分子机制仍未得到充分理解。为了鉴定参与ES发生和发展的候选基因,本研究使用生物信息学方法筛选了与ES相关的关键基因和生物学通路。

方法

从基因表达综合数据库(GEO)下载GSE45544和GSE17618微阵列数据集。鉴定差异表达基因(DEGs)并进行功能富集分析。构建蛋白质-蛋白质相互作用(PPI)网络,并使用STRING和Cytoscape进行关键模块分析。获得一个核心基因,并通过验证数据集GSE67886和免疫组织化学(IHC)进行验证。分别使用ROC方法和Cox回归对ES进行诊断价值和预后评估。

结果

通过将肿瘤样本与正常样本进行比较,共鉴定出187个DEGs,其中包括56个下调基因和131个上调基因。分析了DEGs的富集功能和通路,包括细胞分裂、有丝分裂核分裂、细胞增殖、细胞周期、卵母细胞减数分裂和孕酮介导的卵母细胞成熟。PPI网络中有149个节点和1246条边,根据程度水平鉴定出15个枢纽基因。核心基因()在ES中高表达,通过使用GSE67886和IHC进行验证。ROC分析显示在ES中具有出色的诊断价值(训练集中AUC = 0.75,验证集中AUC = 0.90)。Kaplan-Meier(生存率分析)和Cox回归分析表明,UBE2T是ES患者不良结果的一个标志。

结论

是ES诊断和治疗的重要价值生物标志物,从而为ES提供了一个新的潜在治疗靶点,以及评估治疗效果和预后预测的新视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/bf2f912d8890/fonc-13-1000949-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/5aef6ab37a91/fonc-13-1000949-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/f44b792763c7/fonc-13-1000949-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/b03ad2ce1495/fonc-13-1000949-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/4f21fbc5836e/fonc-13-1000949-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/ee1a3599402f/fonc-13-1000949-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/8e6018746059/fonc-13-1000949-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/bf2f912d8890/fonc-13-1000949-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/5aef6ab37a91/fonc-13-1000949-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/f44b792763c7/fonc-13-1000949-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/b03ad2ce1495/fonc-13-1000949-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/4f21fbc5836e/fonc-13-1000949-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/ee1a3599402f/fonc-13-1000949-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/8e6018746059/fonc-13-1000949-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/071b/9997212/bf2f912d8890/fonc-13-1000949-g007.jpg

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A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination.一种新型的 UBE2T 抑制剂通过阻断 RACK1 泛素化来抑制 Wnt/β-catenin 信号的过度激活和胃癌的进展。
Oncogene. 2021 Feb;40(5):1027-1042. doi: 10.1038/s41388-020-01572-w. Epub 2020 Dec 15.
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The Gene Ontology resource: enriching a GOld mine.基因本体论资源:丰富一个 GOld 矿。
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The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.2021 年的 STRING 数据库:可定制的蛋白质-蛋白质网络,以及用户上传的基因/测量集的功能特征分析。
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UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation.UBE2T 调控的 H2AX 单泛素化通过促进 CHK1 激活诱导肝癌放射抵抗。
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