Correlation Of BUB1 And BUB1B With The Development And Prognosis Of Endometrial Cancer

Objective To investigate the expression and clinical significance of benzimidazole outgrowth inhibition uncoupling homologue protein 1(BUB1)and BUB1 mitotic checkpoint serine/threonine kinase B(BUB1B)in endometrial cancer(EC),and to provide theoretical basis for the diagnosis and treatment of EC.Methods1.Pan-cancer analysis: Bioinformatics was used to analyze the expression of BUB1 and BUB1B genes in different tumors in the TCGA cohort;the prognostic relationship between different tumors with BUB1 and BUB1 B expression levels;the methylation levels in different cancers and adjacent tissues;and the relationship with immune cell infiltration between various tumors.The protein interaction network of BUB1 and BUB1 B related genes was constructed and GO/KEGG enrichment analysis was performed.2.Cellular experiments: BUB1 and BUB1 B genes were silenced in endometrial cancer Ishikawa cell line by si RNA interference technology,and transfection efficiency was detected by q PCR;cell proliferation in each group was detected using CCK8 assay;cell migration was detected by scratch assay;and invasion was detected by Transwell cell invasion assay.One-way ANOVA and LSD-t test were used to compare the data of each group of cells.3.Immunohistochemistry and biochemical analysis: 20 cancer tissues and paracancer tissues of EC patients were collected,and BUB1 and BUB1 B expression were detected by immunohistochemistry;the relationship between BUB1 and BUB1 B and clinical characteristics,prognosis and immune infiltration of endometrial cancer patients was analyzed by bioinformatics.Result1.Pan-cancer analysis: BUB1 and BUB1 B were highly expressed in 26 cancers including BLCA and BRCA.high expression of BUB1 was associated with OS in 8cancers including ACC and KIRC,and with DFS in 10 cancers including ACC and KIRC(P < 0.05).high expression of BUB1 B was associated with OS in 9 cancers including ACC and KIRC,and with DFS in 10 cancers including ACC and KIRC(P <0.05).high expression of BUB1 B was associated with cancers and OS was associated with DFS in 11 cancers including ACC and CHOL(P < 0.05).The methylation level of BUB1 was significantly reduced in cancers such as BLCA and KIRP,and significantly increased in cancers such as ESCA and BRCA(P < 0.05).The methylation level of BUB1 B in cancers such as BLCA and BRCA significantly decreased,and the methylation level of BUB1 B was significantly increased in cancers such as KIRC and2.KIRP(P < 0.05);BUB1 was more frequently altered in melanoma,EC,and bladder cancer gene,mainly by mutation(>5%).BUB1 B was more frequently altered in EC,melanoma gene,mainly by mutation(>5%).BUB1 expression level was associated with BRCA,TGCT CAF infiltration and endothelial cell infiltration of BRCA,KIRC and other cancers,and positively correlated with neutrophil infiltration of COAD and endothelial cell infiltration of KIRP and LGG.BUB1 B expression level negatively correlated with CAF infiltration of BRCA,HNSC-HPV+ and endothelial cell infiltration of BRCA,KIRC and other cancers.BUB1 and BUB1 B and related genes were enriched in the cell cycle of normal and tumor tissues.3.Cellular assay: Ishikawa cells in the BUB1-si RNA group and BUB1B-si RNA group showed significantly decreased proliferation(P < 0.05),migration(P < 0.05)and invasion ability(P < 0.05).3.Biochemical analysis and Immunohistochemical: BUB1 and BUB1 B were highly expressed in EC;high expression of BUB1 correlated with age(P=0.046),histological grade(P<0.001),clinical stage(P<0.001),degree of metastasis(P=0.024),and histological type(P<0.001)of EC patients.high expression of BUB1 B correlated with histological BUB1 B high expression was associated with histological grading(P<0.001),clinical stage(P=0.002),and histological type(P<0.001)of EC patients;BUB1 m RNA high expression significantly shortened OS(P=0.00036)and RFS(P=0.0011)of EC patients.BUB1 B m RNA high expression significantly shortened OS(P=0.0024)of EC patients,but had no effect on RFS No effect(P=0.064);missense mutations,amplifications and profound deletions of BUB1 and BUB1 B gene alterations occurred in 6% of EC.BUB1 expression levels were associated with immune cell infiltration such as activated CD8+ T cells(r =-0.157),activated CD4+ T cells and ADORA2A(r=-0.232),CD244(r=-0.251)and other The expression level of BUB1 B correlated with immune cell infiltration such as CD8+ T cells(r =-0.146),CD4+ T cells(r = 0.556)and immune modulators such as ADORA2A(r =-0.283),CD244(r =-0.232).Conclusion1.BUB1 and BUB1 B and their related genes were enriched in several cancer-related pathways,and BUB1 and BUB1 B were highly expressed in multiple solid tumors and affected prognosis,and were associated with immune infiltration in multiple cancers.2.BUB1 and BUB1 B are highly expressed in EC tissues and affect the development of EC by influencing the proliferation,migration and invasive ability of EC cells.3.The expression of BUB1 and BUB1 B correlated with several clinicopathological features such as EC staging,grading and histological type;BUB1 and BUB1 B were closely related to EC prognosis,immune infiltration and immunomodulators,and are expected to be new prognostic and immunotherapeutic targets.