Transcriptomic Analysis Of The Pathological Mechanism Of NSCLC Based On Combination Of Specific Datasets Of GEO Database

Lung cancer is a common malignant tumor and the first cause of cancer-related deaths worldwide.In China,the proportion of lung cancer patient is already equivalent to that of developed countries,and the non-small cell lung cancer(NSCLC)accounts for 85% of all cases of lung cancer.A large amount of evidence shows that the abnormal expression of certain genes plays a very important role in the process of tumorigenesis,development and metastasis.Therefore,to find differentially expressed genes during the development of non-small cell lung cancer and their related signaling pathways will provide potential targets for the treatment of NSCLC.Our goal is to identify differentially expressed genes(DEGs)and hub genes with related pathways,understanding the pathological mechanism of NSCLC,and find potential biomarkers for diagnosis and treatments.The study was composed of four parts: screening common DEGs,functional enrichment analysis,screening hub genes and results integration.First,four datasets consisting human NSCLC tissues and normal lung tissues gene expression microarray chip data was downloaded from GEO database,then the DEGs in each data set were screened by comparing gene expression of two groups.Through RRA integration of all the DEGs in the four datasets,169 differentially expressed genes were finally obtained,of which 43 were up-regulated and 126 were down-regulated.Then,this experiment enriched the gene ontology(GO)and Kyoto gene and genome encyclopedia(KEGG)pathways of DEGs through DAVID online analysis,respectively,to explored the functions and regulatory pathways involved in the pathogenesis of lung cancer of these 169 common differentially expressed genes.The GO analysis results showed that DEG was mainly free in the cell membrane,extracellular matrix and nucleus,and the biological process was mainly focused on regulating cell proliferation,adhesion,metastasis and angiogenesis as well as intracellular signal cascade,with specific functions concentrated on protein interaction.KEGG pathway analysis showed that these DEGs were mainly involved in ECM receptor interaction,PI3K-Akt signaling pathway,Ras signaling pathway,focal adhesion,etc.Finally,based on the proteinprotein interaction(PPI)network,20 hub genes were screened for Kaplan Meier survival analysis.The results showed that high expression of 7 hub genes,namely ASPM,CDC20,COL1A1,HMMR,NEK2,SPP1 and TOP2 A,was significantly correlated with poor prognosis,and low expression of four hub genes,namely LPL,PECAM1,CDH5 and TEK,was significantly associated with poor prognosis.By combining these hub genes with the KEGG signaling pathway,it can be speculated that the upregulation of COL1A1,HMMR and SPP1 affects the extracellular matrix receptor binding pathway and focal adhesion and activates the PI3K-Akt signaling pathway.The downregulation of TEK reduces the obstacle to angiogenesis and activates the pi3k-akt signaling pathway and the Ras signaling pathway.The activation of pi3k-akt signaling pathway and Ras signaling pathway enables non-small cell lung cancer cells to have abnormal proliferation,angiogenesis,DNA repair and antiapoptosis abilities.In conclusion,the DEGs and hub genes identified in this study may contribute to a comprehensive understanding of the molecular mechanism of NSCLC and may be used as a biomarker for diagnosis and prognosis and as a molecular target for the treatment of non-small cell lung cancer.