The Expression And Prognosis Analysis Of ESPL1 In Lung Adenocarcinoma

BackgroundAdenocarcinoma is the most common pathological type of lung cancer,accounting for 50%of all hung cancers,and its incidence frequency is increasing.There are many treatments for lung adenocarcinoma,including surgery,chemotherapy,radiotherapy,immunization and targeted therapy,which targeted therapy plays a very important role in clinical practice.Although the quality of life for patients is improved after the application of targeted drugs,the survival rate is not significantly improved.Therefore,new genes and corresponding targeted drugs need to improve the survival rate of patients.Extra spindle poles-like 1(ESPL1)gene plays an important role in the development of many cancers.However,the role of ESPL1 in lung adenocarcinoma remains unclear.MethodsThe expression of ESPL1 in all types of tumor was analyzed by TIMER database.Lung adenocarcinoma gene chip data were downloaded from GEO database,its RNA-seq data were downloaded from TCGA database.The expression of ESPL1 in lung adenocarcinoma and among different clinical traits was verified by R software.The expression of ESPL1 protein in lung adenocarcinoma was proved by immunohistochemistry in HPA database,and the localization of ESPL1 in lung adenocarcinoma was investigated by immunofluorescence.The methylation,gene copy number and mutation of ESPL1 were explored in XENA database.Possible upstream regulatory miRNAs of ESPL1 were predicted by StarBase,GEPIA and Kaplan-Meier Plotter databases.Then,the diagnostic value of ESPL1 in lung adenocarcinoma was evaluated by R software,and the prognostic value of ESPL1 in lung adenocarcinoma was evaluated by KM survival analysis and meta-analysis.Univariate and multivariate COX analysis were used to evaluate the independent prognostic value of ESPL1 in lung adenocarcinoma.GSEA analyzed possible downstream regulatory signaling pathways of ESPL1 in lung adenocarcinoma,and verified the relationship between ESPL1 and cell cycle regulation through HPA database.Finally,we evaluated drug sensitivity between ESPL1 and clinical chemotherapeutic drugs through the CellMiner database.ResultsESPL1 was overexpressed in 15 cancers(including lung adenocarcinoma and underexpressed in 2 cancers.In TCGA and 4 GEO data sets,ESPL1 was highly expressed in lung adenocarcinoma tissues compared with normal adjacent tissues,and the expression of ESPL1 increased with the increase of T stage and total TNM stage,which has high diagnostic value.Immunohistochemical staining also showed that ESPL1 protein was highly expressed in lung adenocarcinoma tissues.Immunofluorescence staining showed that ESPL1 was mainly expressed in the nucleus and vesicles.The low expression of hsa-let-7b-5p may negatively regulate ESPL1 expression.TCGA and 5 GEO data sets showed that lung adenocarcinoma patients with high ESPL1 expression had a worse prognosis,which was further verified by Meta analysis,and ESPL1 could be an independent prognostic factor for lung adenocarcinoma patients independent of other clinical traits.GSEA analysis and HPA database results indicated that high expression of ESPL1 may be involved in tumor cell cycle regulation.Sensitivity analysis showed that gefitinib and lapatinib may be targeted agents for lung adenocarcinoma patients with high ESPL1 expression.ConclusionOur study shows that ESPL1 can be used as a molecular indicator for clinical diagnosis and prognosis of lung adenocarcinoma,and it is expected to become a target for prevention and treatment of lung adenocarcinoma.