Expression And Molecular Mechanism Of Kinesin Family Member 20A In Lung Adenocarcinoma

Objective KIF20 A is closely associated with the development of multiple malignancies.This study aims to detect the expression of KIF20 A in lung adenocarcinoma(LUAD)from the protein level and gene transcript level,analyze its relationship with clinicopathological features,and investigate the role of KIF20 A in the occurrence and development of LUAD.Moreover,it is proposed to investigate the mechanism of LUAD invasion and metastasis at the molecular level and to identify the regulatory genes associated with it,which has important implications for further improving the treatment and prognosis of LUAD.Methods1.Evaluation of KIF20 A expression and role in multiple malignancies in TCGA using bioinformatics methods;Tumor tissues and normal paraneoplastic tissues of 27 patients with LUAD undergoing radical lung cancer surgery were selected,and the expression of KIF20 A in the above specimens was detected by Real Time PCR,and immunohistochemistry methods;Regression analysis of parameters affecting prognosis using single-and multifactor Cox proportional risk regression models to determine the effect of KIF20 A expression on patient prognosis.2.Construction of an A549 cell line with low KIF20 A stabilization knockdown to further elucidate the effect of KIF20 A on LUAD development by validating the effect of KIF20 A on LUAD biology and behavior by in vitro experiments;To investigate the regulatory mechanism of KIF20 A in LUAD,we performed bioinformatics analysis of KIF20 A downstream genes and signaling pathways using gene chip technology.3.Screening the KIF20 A gene chip for differential genes using bioinformatics techniques,GO classification and KEGG pathway enrichment analysis of differentially expressed genes of KIF20 A,detection of the effect of KIF20A expression on the signaling pathway in the TCGA database and final screening of genes closely related to KIF20 A.Results1.TCGA database analysis of KIF20 A expression in various human malignant tissues shows that KIF20 A is highly expressed in lung adenocarcinoma and lung squamous carcinoma.2.The expression of KIF20 A in lung cancer tissues and normal paraneoplastic tissues was examined at the m RNA and protein levels using Real Time PCR.The results showed that the expression of KIF20 A at both m RNA and protein levels was higher in lung cancer tissues than in normal paraneoplastic tissue.3.Immunohistochemical results showed that KIF20 A staining was mostly positive in lung cancer tumor,while it was mostly negative or weakly positive in the corresponding paraneoplastic tissue.4.By comparing the clinicopathological parameters in of LUAD in TCGA database,we found the following trends in the high KIF20 A expression group compared to the low KIF20 A expression group: lower age(<65 years),advanced tumor(stage III/IV),lymph node infiltration,higher rate of radiation therapy and positive death.5.By generating Kaplan-Meier curves for OS,PFI,DSS and DFI,we found that high KIF20 A expression was associated with poorer survival outcomes.6.Regression analysis of parameters affecting prognosis using single-and multifactor Cox proportional risk regression models suggests that KIF20 A expression is an independent factor affecting patient prognosis.7.ROC curve results suggest that KIF20 A can be used as a predictive diagnostic indicator for LUAD.8.Knockdown of KIF20 A expression in vitro significantly inhibited the cell proliferation and invasion migration of LUAD cells.9.In LUAD,KIF20 A is involved in cell cycle,cell proliferation,protein transport and other biological processes,mainly related to signaling pathways such as spliceosome,cell cycle and basal transcription factors.10.Genes closely associated with KIF20 A expression were extracted from the TCGA database to form the gene set;the down-regulated genes screened with A549 cells were then used to form the gene set,and the two were taken as cross sets.We found that the genes MKI67,DLGAP5,SPC24,ASPM,SHCBP1,CDC25 C,CENPF were highly expressed in LUAD,which closely associated with poor prognosis and may have synergistic effects with KIF20 A.Conclusion1.KIF20 A is highly expressed in LUAD tissues,and its expression is significantly higher than the corresponding normal lung tissues,and is significantly associated with tumor staging,lymph node metastasis,and poor prognosis,suggesting that KIF20 A plays an important role in the development and progression of LUAD.2.Knockdown of KIF20 A decreases proliferation,migration and invasion capacity of LUAD cells,suggesting that KIF20 A is involved in the malignant biological process of LUAD.3.KIF20 A is mainly involved in cell cycle,cell proliferation,protein translocation and other biological processes in LUAD,which may be related to signaling pathways such as spliceosomes,cell cycle and basic transcription factors,and may have synergistic effects with MKI67,DLGAP5,SPC24 and other cancer genes.