Bioinformatics-based Analysis Of The Role Of BAP18 Gene In Breast Cancer

Objective: According to the latest global cancer statistics,breast cancer has become the first prevalent cancer disease across the world.In recent years,the research on molecular mechanisms of breast cancer and related therapies has been rapidly changing,and we can also see that effective target research is crucial.The bromodomain PHD-finger transcription factor(BPTF)is the largest subunit of the nucleosome remodeling factor(NURF),which is involved in the regulation of chromatin remodeling process and affects cell growth,proliferation,differentiation,and apoptosis.BPTF is the largest subunit of nucleosome remodeling factor(NURF),which is involved in the regulation of chromatin remodeling process and affects cell growth,proliferation,differentiation and apoptosis.The BPTF,BAP18,with a molecular weight of 18 k Da,has been found to be involved in the development of various tumors in recent years.The aim of this study was to investigate the role that BPA18 plays in the process of breast cancer.Methods: The differences of BAP18 gene expression levels between breast cancer tissues and adjacent normal breast tissues were compared using UALCAN and GEPIA databases.Oncomine and UALCAN databases were selected to investigate the expression levels of BAP18 gene in different subtypes of breast cancer.The expression level of BAP18 was assessed in 107 clinical breast cancer patient samples using immunohistochemical staining technology(IHC).The impact of BAP18 gene expression levels on clinical prognosis was statistically analyzed based on the information that collected from follow-up treatment of patients.The protein-protein interaction(PPI)network of BAP18 was constructed using the STRING database,and the results were visualized by Network Analyst software.The functional enrichment analysis of BAP18 was performed by R software and METASCAPE database.In addition,the TCGA database was mined using R software to investigate the correlation of BAP18 gene with the immune checkpoint genes of CTLA4,PD1,and PDL1 in breast cancer.Finally,the immune cell infiltration analysis of BAP18 gene was performed to assess the effect of BAP18 gene on breast cancer microenvironment.Results: The expression level of BAP18 gene was upregulated in breast cancer tissues compared with that of the adjacent normal breast tissues.The expression level of BAP18 gene was significantly higher in ductal carcinoma in situ(DCIS)and triple negative breast cancer(TNBC)than in other subtypes of breast cancer,especially in the TNBC-IM subtype.By functional enrichment analysis,BAP18 gene was significantly associated with the transcriptional process of the nuclear and mitochondrial function of genes in breast cancer cells.By the analysis of immunohistochemical staining results,the expression level of BAP18 was significantly correlated with the pathological indicators of tumor size,lymph node metastasis and molecular typing,while higher expression level of BAP18 gene was associated with worse clinical prognosis,reducing overall survival(OS)and disease-free survival(DFS)of patients.In addition,BAP18 gene was positively correlated with breast cancer immune checkpoint genes such as CTLA4,PD1 and PDL1.By analyzing the level of immune cell infiltration of BAP18 gene,we found that altered expression of BAP18 gene was associated with changes in multiple types of immune cells in the tumor microenvironment and had significant effects on the breast cancer microenvironment.Conclusion: The BAP18 gene might promote the development and progression of breast cancer through its effects on the transcriptional process,tumor cellular metabolic function and tumor microenvironment of breast cancer cells,and the BAP18 gene could be expected to be a new biological research target related to breast cancer research.