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综合转录组分析鉴定出肺腺癌的新型调控因子。

Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma.

作者信息

Mokhlesi Amir, Talkhabi Mahmood

机构信息

Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

出版信息

J Cell Commun Signal. 2020 Dec;14(4):453-465. doi: 10.1007/s12079-020-00565-4. Epub 2020 May 15.

Abstract

Lung adenocarcinoma (LA) is a subtype of lung cancer that accounts for about 40% of all lung cancers. Analysis of molecular mechanisms controlling this cancer can help scientists to detect, control and treat LA. Here, a microarray dataset (GSE118370) containing six normal lung (NL) and six LA samples was screened using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG and ChEA were used to analyze DEGs-related gene ontology, pathways and transcription factors (TFs), respectively. The Protein-protein interaction network for DEGs and TFs was constructed by STRING and Cytoscape. To find microRNAs and metabolites associated with DEGs, miRTarBase and HMDB were used, respectively. It was found that 350 genes were upregulated and 608 genes were downregulated in LA. The upregulated genes or LA-related gens were enriched in biological process and pathways such as extracellular matrix disassembly and p53 signaling pathway, whereas the downregulated genes or NL-related genes were enriched in cell adhesion and cell-surface receptor signaling pathway. ESR1, KIF18B, BIRC5, CHEK1, CCNB1 and AURKA were determined as hub genes for LA. FOXA1 and TFAP2A had the highest number of connectivity in LA-related TFs. hsa-miR-192-5p and hsa-miR-215-5p could target the highest number of LA-related genes. Metabolite analysis showed that Estrone and NADPH were among the top ten metabolites associated with LA-related genes. Taken together, LA-related genes, especially the hub genes, TFs, and metabolites might be used as novel markers for LA, as well as for diagnosis and guiding therapeutic strategies of LA.

摘要

肺腺癌(LA)是肺癌的一种亚型,约占所有肺癌的40%。对控制这种癌症的分子机制进行分析有助于科学家检测、控制和治疗肺腺癌。在此,使用GEO2R筛选了一个包含六个正常肺组织(NL)和六个肺腺癌样本的微阵列数据集(GSE118370),以寻找差异表达基因(DEG)。然后,分别使用DAVID、KEGG和ChEA分析与DEG相关的基因本体、通路和转录因子(TF)。通过STRING和Cytoscape构建了DEG和TF的蛋白质-蛋白质相互作用网络。为了找到与DEG相关的微小RNA和代谢物,分别使用了miRTarBase和HMDB。结果发现,肺腺癌中有350个基因上调,608个基因下调。上调基因或与肺腺癌相关的基因在细胞外基质分解和p53信号通路等生物学过程和通路中富集,而下调基因或与正常肺组织相关的基因在细胞黏附和细胞表面受体信号通路中富集。ESR1、KIF18B、BIRC5、CHEK1、CCNB1和AURKA被确定为肺腺癌的核心基因。FOXA1和TFAP2A在与肺腺癌相关的TF中具有最高的连接数。hsa-miR-192-5p和hsa-miR-215-5p可靶向最多数量的与肺腺癌相关的基因。代谢物分析表明,雌酮和NADPH是与肺腺癌相关基因相关的十大代谢物之一。综上所述,与肺腺癌相关的基因,尤其是核心基因、TF和代谢物,可能用作肺腺癌的新型标志物,以及用于肺腺癌的诊断和指导治疗策略。

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