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基于异常甲基化水平的转录组分析揭示了鼻咽癌潜在的新治疗靶点

英文原题:A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

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A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

PubMed 2022/01/01(内容时间) Ann Transl Med

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研究概要

识别新的重要通路和枢纽基因及其在鼻咽癌发生发展中的作用,将指导临床研究和药物靶点的开发。

研究思路结论见上方概要

本研究旨在通过基于综合生物信息学分析识别异常甲基化-差异表达基因(DEGs)和通路,以确定鼻咽癌(NPC)潜在的新型治疗靶点。

共识别出8个基因表达数据集和2个甲基化微阵列数据集,这些数据集来自Gene Expression Omnibus,包含NPC组和对照组。使用在线分析数据库NetworkAnalyst对DEGs进行meta分析。从GEO2R获得异常甲基化基因位点。从Venn图获得异常甲基化DEGs。在Metascape网站上进行富集分析,并使用Cytoscape软件在String网站上进行蛋白质-蛋白质相互作用(PPI)网络构建、网络分析及分析结果可视化。

共获得544个低甲基化高表达基因和164个高甲基化低表达基因。富集分析和PPI网络分析提示,若干通路和伴随甲基化改变的异常基因表达枢纽基因,包括肌醇三磷酸3激酶B(ITPKB)、G蛋白亚基β5(GNB5)、FYN原癌基因Src家族酪氨酸激酶(FYN)、LCK原癌基因Src家族酪氨酸激酶(LCK)、活化T细胞核因子1(NFATC1)、GNAS复杂位点(GNAS)、蛋白激酶Cβ(PRKCB)、T细胞受体相关蛋白激酶70ζ链(ZAP70)、溶血磷脂酸受体1(LPAR1)、蛋白激酶Cε(PRKCE)、肿瘤蛋白p53(TP53)、甘油醛-3-磷酸脱氢酶(GAPDH)、纤连蛋白1(FN1)、细胞周期蛋白D1(CCND1)、血管内皮生长因子A(VEGFA)、HRas原癌基因GTP酶(HRAS)、信号转导和转录激活因子3(STAT3)、成纤维细胞生长因子2(FGF2)、淀粉样β前体蛋白(APP)和基质金属肽酶2(MMP2),可能与鼻咽癌的发生有关。

展开英文摘要原文

This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis.

Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis database "NetworkAnalyst". Aberrantly methylated gene loci were obtained from the GEO2R. Aberrantly methylated DEGs were obtained from Venn diagrams. The enrichment analysis was carried out on the "Metascape" website, and the protein-protein interaction (PPI) network construction, network analysis, and visualization of the analysis results were carried out on the "String" website using "Cytoscape" software.

In total, 544 hypomethylation high-expression genes and 164 hypermethylation low-expression genes were obtained. The enrichment and PPI network analyses suggested that several pathways and hub genes with abnormal gene expression accompanied by methylation change, including inositol-trisphosphate 3-kinase B ( ITPKB ), G protein subunit beta 5 ( GNB5 ), FYN proto-oncogene, Src family tyrosine kinase ( FYN ), LCK proto-oncogene, Src family tyrosine kinase ( LCK ), nuclear factor of activated T cells 1 ( NFATC1 ), GNAS complex locus ( GNAS ), protein kinase C beta ( PRKCB ), zeta chain of T cell receptor associated protein kinase 70 ( ZAP70 ), lysophosphatidic acid receptor 1 ( LPAR1 ), protein kinase C epsilon ( PRKCE ), tumor protein p53 ( TP53 ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), fibronectin 1 ( FN1 ), cyclin D1 ( CCND1 ), vascular endothelial growth factor A ( VEGFA ), HRas proto-oncogene, GTPase ( HRAS ), signal transducer and activator of transcription 3 ( STAT3 ), fibroblast growth factor 2 ( FGF2 ), amyloid beta precursor protein ( APP ), and matrix metallopeptidase 2 ( MMP2 ), may be related to the occurrence of nasopharyngeal carcinoma .

The identification of novel and important pathways and hub genes and their roles in the occurrence and development of NPC will guide clinical research and the development of pharmaceutical targets.

论文信息

作者
Lyu M、Yi X、Huang Z、Chen Y、Ai Z、Liang Y、Feng Q、Xiang Z
单位
Department of Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China.China
期刊
Annals of translational medicine2022 Jan
原文标识
PubMed 35282089 · DOI 10.21037/atm-21-6628