| Objective: As one of the most common malignant tumors in the urinary system,bladder cancer has a high morbidity rate,which is seriously endangering human health.However,in the past 30 years,the diagnosis and treatment of bladder cancer have not improved significantly,as well as the survival rate of bladder cancer.Early diagnosis is a key point of improving the prognosis of bladder cancer.It is of great significance to find simple and effective diagnostic markers.An increasing number of studies have shown that miRNAs are closely related to the occurrence and development of tumors.In addition,miRNAs still have the potential to be used as tumor diagnostic markers.The miR-17-92 cluster is currently the most widely studied miRNA cluster and has been confirmed to be related to a variety of tumors,including bladder cancer.The purpose of this study is to verify the expression level of miR-17-92 cluster in serum and explore its potential as a non-invasive biomarker for the diagnosis of bladder cancer.Methods: This study first verified the differences in the expression of miR-17-92 clusters in bladder cancer tissues and normal tissues through the TCGA database.In order to evaluate the expression of miR-17-92 cluster in bladder cancer cell lines,this study used RT-q PCR to detect its expression level in bladder cancer cell lines(5637,UM-UC-3,T24,J82,RT-4)and normal human bladder cell line(SV-HUC-1).In order to verify the expression level of miR-17-92 cluster in the sera of bladder cancer patients,this study collected the preoperative sera of 74 patients with bladder cancer and 90 normal control sera.The receiver operating characteristic curve was applied to assess the diagnostic ability of each miRNA,and finally a logistic regression analysis was utilized to select several miRNAs to construct an efficient diagnostic model.In addition,this study obtained GSE113486 dataset from GEO database as an external validation of serum expression of bladder cancer.Results: The 6 members of the miR-17-92 cluster(miR-17-5p,miR-18a-5p,miR-19a-3p,miR-20a-5p,miR-19b-3p and miR-92a-3p)all showed a significantly high expression in bladder cancer tissues,and a significantly high expression in at least one bladder cancer cell line.The expression level of each member of the miR-17-92 cluster in the sera of patients with bladder cancer was significantly higher than that of the normal control group.And some of their expression level were positively correlated with tumor stage and pathological grade.The receiver operating characteristic curve results show that miR-92a-3p(area under curve = 0.902),miR-17-5p(area under curve= 0.845)and miR-20a-5p(area under curve = 0.806)are better diagnostic biomarkers among them.Finally,we use the logistic regression equation to construct a diagnostic model of these 3 miRNAs.The area under the curve of this diagnostic model is 0.969,which has an excellent diagnostic capability.The miR-17-92 cluster members in the GSE113486 dataset were also highly expressed in the serum of bladder cancer patients,which was consistent with the results of this study.Conclusion: The members of the miR-17-92 cluster are highly expressed in bladder cancer tissues,cells and patient serum.The diagnostic model composed of serum miR-92a-3p,miR-17-5p and miR-20a-5p has excellent diagnostic capabilities for bladder cancer and has the potential to be a clinically available non-invasive diagnostic marker. |
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