Research For The Effect About FOXA1 Expression And Immune Infiltrates In Muscle Invasive Bladder Cancer

Objectives:To analyze the difference of FOXA1 expression level and the abundance of immune infiltrates in muscle invasive bladder cancer(MIBC),and to explore the correlation between FOXA1 expression level and immune cell infiltration degree in MIBC.Combined with the analysis of clinical characteristics of MIBC patients,we preliminarily explore the value of FOXA1 and immune cell infiltration in predicting MIBC prognosis,and provide new ideas for further understanding the pathogenesis of bladder cancer and its treatment.Methods:Study the relationship between FOXA1 expression,prognosis and clinical characteristics of MIBC patients via TCGA dataset.Research the relationship between tumor infiltrating immune cells and prognosis was studied via TIMER database,and the correlation between FOXA1 expression and MIBC infiltrating immune cells and their surface markers was analyzed.From January 2015 to December 2018,MIBC patients who underwent radical cystectomy and pelvic lymph node dissection are selected.Patients are from the Department of Urology,Zhongda Hospital and the prostate tissue is obtained from the Department of Pathology.Immunohistochemistry was performed on the postoperative specimens of the included patients,the results and clinical characteristics were analyzed to explore the relationship between FOXA1,tumor infiltrating immune cells and MIBC prognosis.Results:1.Low expression of FOXA1 was correlated with worse OS regardless of the stage T,stage N and gender.2.Based on staining intensity,the tumors were classified into 2 categories as follows: low FOXA1 expression(39cases)and high FOXA1 expression(44cases).Tumors with low FOXA1 expression were associated with higher T stage and more frequent of lymph node invasion compared to those with high FOXA1 expression.3.Low FOXA1 expression is strongly correlated with tumor-associated macrophage and M2 macrophage,high M2 macrophages infiltration are more likely to be higher tumor stage and lymph node metastasis.FOXA1 expression is significantly inversely correlated with markers of tumor-associated macrophage(TAM)and M2 macrophage,but not with markers of M1 macrophage.4.Markers of T cell inactivation and regulatory T cells are negatively correlated with FOXA1 expression.5.Increased infiltrated HLA-DR+ dendritic cells tumor were associated with good prognosis.Conclusion:1.FOXA1 may be a potential prognostic biomarker of MIBC,low FOXA1 expression were associated with worse overall survival.2.FOXA1 may take part in the macrophage polarization to M2 macrophage,M2 macrophage has tumor-promoting roles,which is consistent with our results.3.Low FOXA1 expression may be involved in tumor T cell inactivation,leading to a worse prognosis.4.Tumor infiltrated dendritic cells were associated with lower tumor stage T and lower risk of lymph node metastasis.5.Low FOXA1 expression is a prognostic biomarker of MIBC and immune infiltration level,the level of tumor infiltrated T cell,M2 macrophage and dendritic cell may be potential novel prognostic bio-markers for MIBC.