Expression And Clinical Significance Of LAG-3 In Bladder Urothelial Carcinomaan

Objective: To investigate the expression and clinical significance of LAG-3 in urothelial carcinoma of bladder.Methods: Transcriptional and clinical data of bladder tumors were downloaded from the Cancer Genome Atlas public database((The Cancer Genome Atlas TCGA))to analyze the expression level of LAG-3 in bladder tumors.Differential expression of LAG-3 and CD8+T effector,immune checkpoint,antigen presentation in tumor microenvironment was analyzed.Correlation analysis of LAG-3 with immune cell infiltration and immune genes in tumor;A total of 71 patients who underwent radical resection of bladder tumor or partial resection of bladder tumor in Ningxia Medical University Hospital from July 2014 to July2022 and were pathologically diagnosed as urothelial carcinoma were enrolled,including 44 patients with muscular invasive bladder tumor and 27 patients with non-muscular invasive bladder tumor.The correlation between the positive expression of LAG-3 and the general clinical data was analyzed through IHC staining of the paraffin tissue of patients with bladder tumor.The positive expression of LAG-3 and the general clinical data were analyzed by variance.The Chi-square test of LAG-3 and pathological grade was analyzed.Clinical prognostic data of LAG-3 factors were analyzed,Kaplan-Meier method was used,and survival curve was drawn.Results: 1.Analysis of TCGA public database showed that LAG-3 was significantly expressed in bladder tumors and was correlated with the pathological grade of tumors.The higher the grade,the more obvious the differential expression(P<0.05),In the bladder tumor microenvironment,the high and low expression of LAG-3 was significantly different from the effector of CD8-T,antigen processing mechanism,mismatch repair,nucleotide excision repair,DNA damage response,etc.(P<0.05).The high and low expression of LAG-3 had statistical significance on the differential expression of dendritic cells,regulatory T cells,macrophages,mucosa-associated constant T cells,monocytes,neutrophils,and other immune cells(P<0.05).LAG-3 and immune checkpoint PD-L1,PDCD-1,CTLA-4,TIGIT were positively correlated.2.In immunohistochemical experiments,the differentially expressed LAG-3 was statistically significant in urinary urothelial carcinoma and Para cancer(P<0.05),and the expression rate was 32%.3.After strict follow-up of 71 patients,COX multivariate analysis showed that LAG-3and clinical stage were independent risk factors for bladder tumor,and LAG-3Kaplan-Meier survival curve analysis showed that patients with positive LAG-3 expression had poor survival prognosis(P < 0.05).4.After strict follow-up of 71 patients,COX univariate and multivariate analysis showed clinical stage and independent risk factors of LAG-3 bladder tumor,and LAG-3Kaplan-Meier survival curve analysis showed that patients with positive LAG-3 expression had poor survival prognosis(P < 0.05).Conclusion: LAG-3 may be a risk factor for bladder cancer progression and invasion.LAG-3 expression and clinical stage are independent risk factors for the prognosis of bladder cancer,and LAG-3 can be used as a marker for the diagnosis and prognosis of bladder cancer.