AP1S1 Expression In Breast Cancer And Its Correlation With Clinical Factors

Objectives:AP1S1(Adaptor related protein complex 1 subunit sigma 1)has been reported to be associated with the progression of malignant tumors in previous studies,but there is no comprehensive bioinformatics analysis in breast cancer.In this study,the clinicopathological characteristics and potential diagnostic and prognostic value of AP1S1 in breast cancer were comprehensively studied.Methods:The differentially expressed genes in breast cancer were retrieved using GEPIA database and the target single gene AP1S1 was screened.The expression of AP1S1 in tumor lineages and breast cancer tissues and cells was verified using the human protein atlas.The correlation between AP1S1 gene expression level and promoter methylation level and clinicopathological features of breast cancer was analyzed by UALCAN database,and genes positively correlated with AP1S1 expression in breast cancer were screened,and pathway enrichment analysis was performed by Metascape.The correlation between AP1S1 and tumor-infiltrating immune cells in breast cancer tissues was analyzed through TIMER database.Finally,Kaplan-Meier Plotter was used to draw the survival curve of breast cancer patients.Results:Through GEPIA database search,AP1S1 was found to be differentially expressed in breast cancer and correlated with prognosis.However,there is no comprehensive bioinformatics analysis at present,so it is the single gene targeted for this study.The human protein atlas verified the expression of AP1S1 in breast cancer tissues and cells,and the results showed that AP1S1 was low expressed in adipose cells of normal breast tissue specimens and medium expressed in glandular epithelial cells,while no AP1S1 protein was detected in myoepithelial cells.AP1S1 was moderately expressed in invasive ductal carcinoma and invasive lobular carcinoma.Immunocytochemical analysis showed that the fluorescent labeling of AP1S1 was mainly distributed in the Golgi apparatus and vesicles of MCF-7 cell line.UALCAN database analysis showed that the expression level of AP1S1 in breast cancer tissues was higher than that in normal breast tissues(P<0.05).The expression level of AP1S1 gene in stageⅣbreast cancer was higher than that in stageⅠ,ⅡandⅢbreast cancer(P<0.05).The expression level of AP1S1 gene in triple negative and HER2 overexpressed breast cancer was higher than that in hormone receptor-positive breast cancer(P<0.05).Analysis of methylation level of AP1S1 promoter showed that the methylation level in breast cancer tissues was lower than that in normal tissues(P<0.05).In different breast cancer subgroups,the promoter methylation level of AP1S1 in stageⅡandⅢwas higher than that in stageⅣbreast cancer(P<0.05),and the promoter methylation level of HER2 overexpressed breast cancer and triple negative breast cancer was lower than that in hormone receptor-positive breast cancer(P<0.05).Promoter methylation levels were higher in breast cancer patients aged 61 to 80 years than in patients aged 21 to 60 years(P<0.05).149 genes were found to be positively correlated with AP1S1 expression in breast cancer by UALCAN database retrieval(Pearson-CC≥0.3).The results of pathway enrichment analysis showed that the replication initiation recognition complex,DNA replication,nc RNA metabolism and protein targeted transport were significantly enriched(P<0.05).Tumor immunoassay analysis showed that AP1S1 was positively correlated with the invasion levels of myeloid suppressor cells and regulatory T cells(Rho>0,P<0.05),and negatively correlated with the invasion levels of CD4~+T cells,CD8~+T cells,hematopoietic stem cells and neutrophils(Rho<0,P<0.05).Kaplan-Meier Plotter analysis showed that breast cancer patients with high AP1S1 expression had poorer overall survival(Logrank P=0.035,HR=1.28).Conclusion:The expression level of AP1S1 in breast cancer tissues is higher than that in normal tissues,and is related to the severity of the disease.Breast cancer patients with high AP1S1 expression have a worse prognosis.Therefore,AP1S1 can be used as a biomarker for diagnosis and prognosis of breast cancer patients.