Meta-Analysis of EGF-Stimulated Normal and Cancer Cell Lines to Discover EGF-Associated Oncogenic Signaling Pathways and Prognostic Biomarkers.

IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Shahrokh Garousi, Sodabeh Jahanbakhsh Godehkahriz, Kasra Esfahani, Tahmineh Lohrasebi, Amir Mousavi, Ali Hatef Salmanian, Mahsa Rezvani, Maryam Moein
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引用次数: 2

Abstract

Background: Although epidermal growth factor (EGF) controls many crucial processes in the human body, it can increase the risk of developing cancer when overexpresses.

Objectives: This study focused on detecting cancer-associated genes that are dysregulated by EGF overexpression.

Materials and methods: To identify differentially expressed genes (DEGs), two independent meta-analyses with normal and cancer RNA-Seq samples treated by EGF were conducted. The new DEGs detected only via two meta-analyses were used in all downstream analyses. To reach count data, the tools of FastQC, Trimmomatic, HISAT2, SAMtools, and HTSeq-count were employed. DEGs in each individual RNA-Seq study and the meta-analysis of RNA-Seq studies were identified using DESeq2 and metaSeq R package, respectively. MCODE detected densely interconnected top clusters in the protein-protein interaction (PPI) network of DEGs obtained from normal and cancer datasets. The DEGs were then introduced to Enrichr and ClueGO/CluePedia, and terms, pathways, and hub genes enriched in Gene Ontology (GO) and KEGG and Reactome were detected.

Results: The meta-analysis of normal and cancer datasets revealed 990 and 541 new DEGs, all upregulated. A number of DEGs were enriched in protein K48-linked deubiquitination, ncRNA processing, ribosomal large subunit binding, and protein processing in endoplasmic reticulum. Hub genes overexpression (DHX33, INTS8, NMD3, OTUD4, P4HB, RPS3A, SEC13, SKP1, USP34, USP9X, and YOD1) in tumor samples were validated by TCGA and GTEx databases. Overall survival and disease-free survival analysis also confirmed worse survival in patients with hub genes overexpression.

Conclusions: The detected hub genes could be used as cancer biomarkers when EGF overexpresses.

Abstract Image

Abstract Image

Abstract Image

对egf刺激的正常和癌细胞系进行荟萃分析,发现egf相关的致癌信号通路和预后生物标志物。
背景:虽然表皮生长因子(EGF)控制着人体的许多关键过程,但当其过度表达时,会增加患癌症的风险。目的:本研究的重点是检测因EGF过表达而失调的癌症相关基因。材料和方法:为了鉴定差异表达基因(DEGs),我们对经EGF处理的正常和癌症RNA-Seq样本进行了两项独立的荟萃分析。仅通过两项荟萃分析检测到的新deg用于所有下游分析。为了获得计数数据,我们使用了FastQC、Trimmomatic、HISAT2、SAMtools和HTSeq-count等工具。分别使用DESeq2和metaSeq R包对每个RNA-Seq研究和RNA-Seq研究的荟萃分析中的deg进行鉴定。MCODE检测了从正常和癌症数据集中获得的deg蛋白蛋白相互作用(PPI)网络中紧密相连的顶部簇。然后将deg引入到enrichment和ClueGO/CluePedia中,检测基因本体(GO)和KEGG和Reactome中富集的术语、途径和枢纽基因。结果:对正常和癌症数据集的荟萃分析显示,990和541个新的deg均上调。许多deg在蛋白质k48相关的去泛素化、ncRNA加工、核糖体大亚基结合和内质网蛋白质加工中富集。通过TCGA和GTEx数据库验证肿瘤样本中Hub基因(DHX33、INTS8、NMD3、OTUD4、P4HB、RPS3A、SEC13、SKP1、USP34、USP9X、YOD1)的过表达。总生存期和无病生存期分析也证实hub基因过表达患者的生存期较差。结论:检测到的枢纽基因可作为EGF过表达时的肿瘤生物标志物。
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来源期刊
Iranian Journal of Biotechnology
Iranian Journal of Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
2.60
自引率
7.70%
发文量
20
期刊介绍: Iranian Journal of Biotechnology (IJB) is published quarterly by the National Institute of Genetic Engineering and Biotechnology. IJB publishes original scientific research papers in the broad area of Biotechnology such as, Agriculture, Animal and Marine Sciences, Basic Sciences, Bioinformatics, Biosafety and Bioethics, Environment, Industry and Mining and Medical Sciences.
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