Screening Of Differentially Expressed Genes And Study Of Targeted Drugs In Small Cell Lung Cancer

Objective:The purpose of this study was to identify differentially expressed genes(DEGs)in Small Cell Lung Cancer(SCLC),to annotate the biological functions and abnormally regulated signaling pathways,and to explore the core driver genes of SCLC.Explore SCLC's targeted drugs and verificate its treatment effect in vitro at the same time.Methods:Based on the m RNA expression profile data of GSE40275 and GSE43346 and bioinformatics methods,Gene Spring software was used to identify DEGs between SCLC and normal lung tissues.GO(Gene Ontology)analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis were performed to annotate the biological functions of differentially expressed genes.At the same time,a protein-protein interaction(PPI)network was constructed to identify SCLC core driving risk genes.In addition,in vitro cell experiments such as MTT assay,clone formation experiment,and scratch test were performed to verify the antitumor effect of the drug.Results:A total of 305 tumor-associated DEGs were screened from SCLC tissues,of which 129 genes were up-regulated and 176 genes were down-regulated.Among all DEGs,KIF11,NDC80,and PBK were identified as core-driven DEGs.The results of real-time quantitative reverse transcription PCR in vitro showed that the expression of KIF11,NDC80,and PBK in SCLC cells were significantly higher than that in normal lung tissue cell lines(P = 0.001).Monastrol,a small molecule inhibitor targeting the KIF11 gene,showed good antitumor effects in MTT assays,clone formation experiments,and scratch experiments,inhibited SCLC cell viability,and hindered tumor cell proliferation and migration(P = 0.001).Conclusion:1.KIF11,NDC80 and PBK may be the core driver genes of SCLC,which are worthy of further study.2.Monastrol effectively inhibits SCLC cell proliferation and migration in vitro and is a potential targeted specific drug for treating SCLC patients,which deserves further study.3.SCLC up-regulated differentially expressed genes are enriched in cell division processes,sister chromatid agglutination biological processes,and nuclear components.These changes are conducive to the preparation of DNA replication,promote the self-replication of SCLC cells,and abnormal SCLC tumor cells The ability of malignant proliferation reduces the sensitivity of cells to inhibitory growth signals.4.The excessive activation of the Fanconi anemia pathway plays an important role in the occurrence and development of SCLC.5.SCLC down-regulated differentially expressed genes are enriched in vasoconstriction-related proteins,and continuous blood supply provides sufficient nutrients for tumor tissue growth.Changes in the composition of the outer cell membrane affect the identification and signal transmission between SCLC tumor cells,and at the same time promote the migration of tumor cells.At the same time,immune recognition receptor activity is inhibited,causing the body to fail to recognize and clear abnormal cells,further leading to SCLC.