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Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma.
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2020-05-15 , DOI: 10.1007/s12079-020-00565-4
Amir Mokhlesi 1 , Mahmood Talkhabi 1
Affiliation  

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.

中文翻译:

全面的转录组分析确定了肺腺癌的新型调节剂。

肺腺癌(LA)是肺癌的一种亚型,约占所有肺癌的40%。分析控制这种癌症的分子机制可以帮助科学家发现,控制和治疗LA。在这里,使用GEO2R筛选了包含六个正常肺(NL)和六个LA样品的微阵列数据集(GSE118370),以找到差异表达的基因(DEG)。然后,分别使用DAVID,KEGG和ChEA分析与DEGs相关的基因本体,途径和转录因子(TF)。DEG和TF的蛋白质-蛋白质相互作用网络由STRING和Cytoscape构建。为了找到与DEG相关的microRNA和代谢物,分别使用了miRTarBase和HMDB。发现在LA中350个基因被上调而608个基因被下调。上调的基因或LA相关基因在细胞外基质分解和p53信号通路等生物学过程和途径中富集,而下调的基因或NL相关基因在细胞粘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LA的中枢基因。在洛杉矶相关的TF中,FOXA1和TFAP2A具有最高的连接数。hsa-miR-192-5p和hsa-miR-215-5p可以靶向最高数量的LA相关基因。代谢物分析表明,雌酮和NADPH是与LA相关基因相关的十大代谢物。两者合计,LA相关基因,特别是毂基因,TFs和代谢产物可能被用作LA的新标记,以及LA的诊断和指导治疗策略。
更新日期:2020-05-15
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