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基于生物信息学的骨肉瘤肺转移关键基因及功能鉴定

[Identification of key genes and functions in lung metastasis of osteosarcoma based on bioinformatics].

作者信息

Wang Xin, Peng Li-Hua, Chen Xing-Wang

机构信息

Department of Orthopaedics, Bishan Hospital of Chongqing Medical University, Chongqing 402760, China.

出版信息

Zhongguo Gu Shang. 2024 Jul 25;37(7):718-24. doi: 10.12200/j.issn.1003-0034.20221326.

Abstract

OBJECTIVE

To screen the differentially expressed genes of lung metastasis of osteosarcoma by bioinformatics, and explore their functions and regulatory networks.

METHODS

The data set of GSE14359 was screened from GEO database(http://www.ncbi.nlm.nih.gov/gds) and the differentially expressed gene(DEG) was identified using GEO2R online tool. Download osteosarcoma disease related miRNAs from the online HMMD database(http://www.cuilab.cn/hmdd) and then FunRich software was used to predict the target gene, intersects with DEG to obtains the target gene. The miRNA-mRNA relationship pairs were formed according to the targeted joints, then the data was imported into Cytoscape for visualization, DAVID was used to performe GO and KEGG analysis on target genes, STRING was used to construct PPI network, Cytoscape visualization, CytoHubba plug-in screening central genes and online website for expression and survival analysis.

RESULTS

Total 704 DEGs were identified, consisting of 477 up-regulated genes and 227 down regulated genes. FunRich predicted 7 888 mRNAs and 343 target genes were obtained through intersection of the two. KEGG analysis showed that it was mainly involved in focal adhesion, ECM receptor interaction, TNF signal pathway, PI3K-Akt signal pathway, IL-17 signal pathway and MAPK signal pathway. Ten central genes (CCNB1, CHEK1, AURKA, DTL, RRM2, MELK, CEP55, FEN1, KPNA2, TYMS) were identified as potential key genes. Among them, CCNB1, DTL, MELK were highly correlated with poor prognosis.

CONCLUSION

The key genes and functional pathways identified in this study may be helpful to understand the molecular mechanism of the occurrence and progression of lung metastases from osteosarcoma, and provide potential therapeutic targets.

摘要

目的

通过生物信息学方法筛选骨肉瘤肺转移的差异表达基因,并探究其功能及调控网络。

方法

从GEO数据库(http://www.ncbi.nlm.nih.gov/gds)筛选GSE14359数据集,使用在线工具GEO2R鉴定差异表达基因(DEG)。从在线HMMD数据库(http://www.cuilab.cn/hmdd)下载骨肉瘤相关miRNA,然后用FunRich软件预测靶基因,与DEG进行交集分析以获得靶基因。根据靶向关系形成miRNA-mRNA关系对,将数据导入Cytoscape进行可视化,用DAVID对靶基因进行GO和KEGG分析,用STRING构建PPI网络,Cytoscape可视化,使用CytoHubba插件筛选核心基因并通过在线网站进行表达和生存分析。

结果

共鉴定出704个DEG,其中477个上调基因和227个下调基因。FunRich预测了7888个mRNA,通过两者交集获得343个靶基因。KEGG分析表明其主要涉及粘着斑、细胞外基质受体相互作用、TNF信号通路、PI3K-Akt信号通路、IL-17信号通路和MAPK信号通路。鉴定出10个核心基因(CCNB1、CHEK1、AURKA、DTL、RRM2、MELK、CEP55、FEN1、KPNA2、TYMS)为潜在关键基因。其中,CCNB1、DTL、MELK与预后不良高度相关。

结论

本研究鉴定出的关键基因和功能通路可能有助于理解骨肉瘤肺转移发生和进展的分子机制,并提供潜在治疗靶点。

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