Integrated analysis of hub genes and intrinsically disordered regions in triple-negative breast cancer

IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology
Azhar Iqbal , Faisal Ali , Sulaiman Ali Alharbi , Muhammad Sajid , Saleh Alfarraj , Momina Hussain , Tehmina Siddique , Rakhshanda Mustaq , Fakhra Shafique , Muhammad Sarfaraz Iqbal
{"title":"Integrated analysis of hub genes and intrinsically disordered regions in triple-negative breast cancer","authors":"Azhar Iqbal ,&nbsp;Faisal Ali ,&nbsp;Sulaiman Ali Alharbi ,&nbsp;Muhammad Sajid ,&nbsp;Saleh Alfarraj ,&nbsp;Momina Hussain ,&nbsp;Tehmina Siddique ,&nbsp;Rakhshanda Mustaq ,&nbsp;Fakhra Shafique ,&nbsp;Muhammad Sarfaraz Iqbal","doi":"10.1016/j.jgeb.2024.100408","DOIUrl":null,"url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) is the most prevalent breast cancer subtype. Its prognosis is poor because there are no effective treatment targets. Despite several attempts, the molecular pathways of TNBC remain unknown, posing a significant clinical barrier in the search for viable targets. Two microarray datasets were used to identify possible targets for TNBC, GSE38959 and GSE45827, retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in TNBC samples compared with normal samples were identified using the GEO2R program. KEGG pathway enrichment and Gene Ontology functions were assessed for DEG pathways and functional annotation using ShinyGO 0.77. The STRING database and Cytoscape program were used for protein-protein interaction (PPI) analysis. Furthermore, we evaluated the predictive significance of hub gene expression in TNBC patients using the GEPIA2 online tool. We developed a comprehensive technique to assess whether intrinsically disordered regions (IDRs) are present in the TNBC hub genes. There were 48 DEGs were identified, all of which were upregulated. A putative protein complex containing these four core genes was selected for further analysis. Breast cancer patients with TTK, TOP2A, CENPF, and CCNA2 upregulation had a poor prognosis; TTK and CCNA2 were partially disordered, whereas TOP2A and CENPF were primarily disordered, according to IDR analysis. According to our study, TOP2A and CENPF may be useful therapeutic targets for disruption of the TNBC PPI network.</p></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1687157X24001112/pdfft?md5=ad04e53bf476dff625423ed5e7bb0542&pid=1-s2.0-S1687157X24001112-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Genetic Engineering and Biotechnology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1687157X24001112","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) is the most prevalent breast cancer subtype. Its prognosis is poor because there are no effective treatment targets. Despite several attempts, the molecular pathways of TNBC remain unknown, posing a significant clinical barrier in the search for viable targets. Two microarray datasets were used to identify possible targets for TNBC, GSE38959 and GSE45827, retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in TNBC samples compared with normal samples were identified using the GEO2R program. KEGG pathway enrichment and Gene Ontology functions were assessed for DEG pathways and functional annotation using ShinyGO 0.77. The STRING database and Cytoscape program were used for protein-protein interaction (PPI) analysis. Furthermore, we evaluated the predictive significance of hub gene expression in TNBC patients using the GEPIA2 online tool. We developed a comprehensive technique to assess whether intrinsically disordered regions (IDRs) are present in the TNBC hub genes. There were 48 DEGs were identified, all of which were upregulated. A putative protein complex containing these four core genes was selected for further analysis. Breast cancer patients with TTK, TOP2A, CENPF, and CCNA2 upregulation had a poor prognosis; TTK and CCNA2 were partially disordered, whereas TOP2A and CENPF were primarily disordered, according to IDR analysis. According to our study, TOP2A and CENPF may be useful therapeutic targets for disruption of the TNBC PPI network.

综合分析三阴性乳腺癌中的枢纽基因和内在紊乱区
三阴性乳腺癌(TNBC)是最常见的乳腺癌亚型。由于没有有效的治疗靶点,其预后很差。尽管进行了多次尝试,但 TNBC 的分子通路仍然未知,这对寻找可行的靶点构成了重大的临床障碍。我们使用了从基因表达总库(GEO)数据库中检索到的两个微阵列数据集(GSE38959 和 GSE45827)来确定 TNBC 的可能靶点。使用 GEO2R 程序鉴定了 TNBC 样本与正常样本相比的差异表达基因(DEGs)。使用 ShinyGO 0.77 对 DEG 通路和功能注释的 KEGG 通路富集和基因本体功能进行了评估。STRING 数据库和 Cytoscape 程序用于蛋白质-蛋白质相互作用(PPI)分析。此外,我们还使用 GEPIA2 在线工具评估了 TNBC 患者中枢基因表达的预测意义。我们开发了一种综合技术来评估 TNBC 中心基因中是否存在内在紊乱区(IDR)。共鉴定出 48 个 DEGs,所有这些 DEGs 都是上调的。研究人员选择了包含这四个核心基因的假定蛋白复合物进行进一步分析。根据IDR分析,TTK、TOP2A、CENPF和CCNA2上调的乳腺癌患者预后较差;TTK和CCNA2部分紊乱,而TOP2A和CENPF主要紊乱。根据我们的研究,TOP2A和CENPF可能是破坏TNBC PPI网络的有用治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Genetic Engineering and Biotechnology
Journal of Genetic Engineering and Biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
5.70
自引率
5.70%
发文量
159
审稿时长
16 weeks
期刊介绍: Journal of genetic engineering and biotechnology is devoted to rapid publication of full-length research papers that leads to significant contribution in advancing knowledge in genetic engineering and biotechnology and provide novel perspectives in this research area. JGEB includes all major themes related to genetic engineering and recombinant DNA. The area of interest of JGEB includes but not restricted to: •Plant genetics •Animal genetics •Bacterial enzymes •Agricultural Biotechnology, •Biochemistry, •Biophysics, •Bioinformatics, •Environmental Biotechnology, •Industrial Biotechnology, •Microbial biotechnology, •Medical Biotechnology, •Bioenergy, Biosafety, •Biosecurity, •Bioethics, •GMOS, •Genomic, •Proteomic JGEB accepts
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信