Comprehensive Analysis Of The Expression,Function And Prognostic Value Of PTTG1 In Non-Small Cell Lung Cancer

Objective:1.To explore the expression difference of PTTG1 in lung tissues of patients with non-small cell lung cancer（NSCLC）and normal controls,and to investigate its value in lung cancer stage and prognosis evaluation;2.Explore the expression,association and possible molecular pathways of PTTG1 and its co-expressed genes in NSCLC;3.To study the effect of PTTG1 on proliferation,migration and invasion of NSCLC cells.Methods:Uniprot,Multiple Sequence Alignment by CLUSTALW,ESPript3,SMART,Clustal Omega databases were used to analyze the conservatism of PTTG1 in different species.HPA,UALCAN,Oncomine,GEPIA,Kaplan-Meier Plotter databases were used to obtain the expression difference of PTTG1 in lung tissues of NSCLC patients and normal controls,and its value in lung cancer stage and prognosis evaluation was further analyzed.cBioPortal database was used to obtain PTTG1 mutations and co-expressed genes in lung adenocarcinoma,and Cytoscape tool was used for protein interaction analysis（PPI）.DAVID website was used for GO and KEGG enrichment analysis of PTTG1 gene and its top 100 co-expressed genes in lung adenocarcinoma.In addition,PTTG1 was knocked down in A549,H1650 and H1299 cells,and the effects of knockdown PTTG1 on MMP9,Twistl,Ki67,TGF-β,Snail,Slug and Hes1 were detected by q-PCR.Our research group also verified the effect of knockdown PTTG1 on migration and proliferation of NSCLC cells through scratch test and CCK-8 test.Results:1.Multiple database analyses indicated:PTTG1 was highly expressed in NSCLC tissues compared with normal lung tissues,but there was no significant difference among different stages.In addition,high PTTG1 expression is associated with poor prognosis in lung cancer patients.2.By analyzing the coexpression genes of PTTG1,our team found 10 key genes（hub genes）:NCAPH,BIRC5,DLGAP5,NCAPG,CDCA5,CCNB1,CDK1,KIF11,TPX2,and BUB1.GO and KEGG analysis showed that PTTG1 and its co-expressed gene enrichment were mainly involved in regulating mitosis,chromosome separation,DNA replication and P53 signaling pathways.3.q-PCR showed that PTTG1 knockdown in A549,H1650 and H1299 cells could inhibit MMP9 expression;The scratch test and CCK-8 test showed that knocking down PTTG1 could inhibit the migration and proliferation of NSCLC cells.Conclusion:PTTG1 is highly expressed in NSCLC and is associated with poor prognosis of patients.Knockdown of PTTG1 expression can inhibit MMP9 expression and inhibit NSCLC cell migration and proliferation.