Prognostic Significance Of Matrix Metalloproteinases (MMPs) In Bladder Cancer

ObjectivesThe expression of MMP family in bladder cancer and its influence on prognosis were studied by applying public biological data platform.MethodsThe MMP family-related data of bladder cancer patients were obtained from TCGA database platform.The Kaplan-Meier Plotter platform was used to evaluate the prognosis and survival analysis of MMP family in bladder cancer patients.The survival curve was made to compare the difference of total survival time(OS)and progression-free survival time(RFS)of bladder cancer patients with high and low expression of MMP family members.Multivariate regression analysis was carried out on different MMP family members to further screen differential genes.The prognostic value of MMP family in bladder cancer was analyzed by Surv Express platform.To study m RNA expression of MMP family in normal tissues and bladder cancer tissues on GEPIA platform.The protein expression of MMP family in bladder cancer tissues and normal bladder mucosa was analyzed by human protein atlas.The TIMER platform was used to analyze the relationship between MMP family differential gene expression in bladder cancer and tumor immune infiltrating cells(TIICs).Finally,the clinical pathological information of patients obtained by TCGA,the expression level and risk grade of MMP gene after screening are combined into a multi-gene prognosis model,and single-factor and multi-factor Cox regression analysis is carried out to analyze the influencing factors of survival and prognosis of bladder cancer patients,so as to verify the prognostic value of MMP family in bladder cancer patients.ResultsThe survival prognosis of MMP family was analyzed by Kaplan-Meier Plotter platform.The high expression of 9 groups of MMP(MMP2,MMP8,MMP9,MMP11,MMP13,MMP14,MMP16,MMP17,MMP24)was associated with lower OS(P value?0.05).The high expression of MMP(MMP10,MMP15,MMP20,MMP21,MMP23 A,MMP26,and MMP28)in 7 groups is related to higher OS(P value?0.05).the high expression of MMP10 and MMP24 shows poor RFS,while the high expression of MMP(MMP2,MMP7,MMP9,MMP15,MMP25,and MMP27)in 7 groups is related to higher RFS(P value?0.05).Four groups of MMP were selected from MMP family with differential expression through multifactorial analysis: MMP9,MMP16,MMP17,MMP28,suggesting that it is closely related to the prognosis of bladder cancer.The risk curve of MMP differential genes was obtained by Surv Express platform.MMP family members were associated with higher risk and poorer survival(P value? 0.05).The m RNA expression of the screened gene in bladder tumor tissue and normal tissue was analyzed on the platform of GEPIA.The m RNA expression of MMP9 in tumor tissue was significantly higher than that in normal tissue.MMP9,MMP16 and MMP17 m RNA expressions in high-grade bladder cancer were significantly higher than those in low-grade bladder cancer.According to the human protein map,there are significant differences in protein expression between MMP9 and MMP16.The expression of MMP9 was negatively correlated with the purity of bladder cancer tumor(COR =-0.052,P = 9.44E31),positively correlated with CD4+T cells(COR = 0.321,P = 3.52E10),neutrophils(COR = 0.371,P = 2.89E13)and dendritic cells(COR = 0.483,P =9.35E23).The expressions of MMP16,MMP17 and MMP28 have no significant correlation with the purity of bladder cancer tumor and tumor immune infiltrating cells.The basic information of bladder cancer patients downloaded from TCGA database and the target gene expression after screening,the patients' high and low risks are integrated into a multi-gene prognosis model,and single-factor and multi-factor Cox survival analysis is carried out.the results of single-factor Cox regression model analysis show that age,stage,primary tumor t,lymph node metastasis MMP9,MMP16,MMP17 gene expression,and patient risk assessment are all related to the prognosis and survival ofbladder cancer(P value?0.05).Further,the factors affecting the prognosis of bladder cancer were included in the multivariate Cox regression model analysis.the results showed that age,lymph node metastasis MMP9,MMP16 gene expression were closely related to the prognosis of bladder cancer and can be used as independent influencing factors for the prognosis of bladder cancer patients(P value?0.05).ConclusionMMP family has a variety of biological functions in the progression of bladder cancer.MP9 and MMP16 can be used as independent prognostic factors to predict the prognosis of bladder cancer patients,providing corresponding references for further research on the pathogenesis of bladder cancer,biological indicators for early diagnosis of bladder cancer and possible target therapy of bladder cancer.