Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma
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Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma Amir Mokhlesi 1 & Mahmood Talkhabi 1 Received: 24 March 2020 / Accepted: 30 March 2020 # The International CCN Society 2020
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. Keywords Lung adenocarcinoma . Protein–protein interaction . Bioinformatics analysis . Transcription factor . miRNA . Metabolite
Introduction Lung cancer is a highly heterogeneous malignant epithelial tumor that is one of the most dangerous cancers that kill more than one million people of both sex each year (Chen et al. 2018). Approximately 50% of patients diagnosed with lung cancer die in the first year after diagnosis and the 5-year survival is < 20% (Howlader et al. 2015). Approximately 85% of lung cancer cases are diagnosed as non-small cell lung cancers (NSCLC), which are subdivided to squamous cell carcinoma (SCC), lung adenocarcinoma (LA) and large cell carcinoma (LCC) subtypes (Ettinger et al. 2018). Among them, LA
* Mahmood Talkhabi [email protected] 1
Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
accounts for 40% of all lung cancers and it is the most prevalence lung cancer in people who have never smoked (de Groot et al. 2018). Unfortunately, despite of different treatment options such as surgery, chemotherapy and radiotherapy for LA patients, but the five-year survival rate remain
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