A Novel Biomarker Based on miRNA to Predict the Prognosis of Muscle-Invasive Bladder Urothelial Carcinoma.

Yueyi Feng,Fang Meng,Qingting Feng,Xiaochen Shu,Yiqing Jiang,Lingkai Xu

doi:10.1155/2019/2654296

Abstract

Muscle-invasive bladder urothelial carcinoma (MIBC) is characteristic of high mortality and high recurrence. Distinguishing the prognostic risk of MIBC at the molecular level of miRNA expression is rarely performed and thus of great significance for the management and treatment of MIBC in clinics. Adaptive lasso Cox's proportional hazards model was used to explore the relationship between differential expression miRNAs (DEmiRNAs) and MIBC survival. Furthermore, we evaluated the epithelial-mesenchymal transition (EMT) score and immune infiltration abundance by exploring EMT signature genes and TIMER database, respectively. A total of 8 DEmiRNAs were detected to be associated with the survival rate of MIBC by using the lasso Cox algorithm. Through the linear combination of these 8 DEmiRNAs, we constructed a calculated marker, which could be used to distinguish the prognosis risk in both TCGA dataset (HR = 2.03, 95% CI = (1.47, 2.83)) and independent validation dataset (HR = 7.74, 95% CI = (1.05, 56.93)). Meanwhile, the constructed marker had reasonably high predictive values of the AUC (area under the curve) in the TCGA dataset and validation dataset being 0.73 and 0.63, respectively. In addition, we observed that the expression values of let-7c, miR-100, and miR-145 were associated with EMT score and the abundance of macrophage in tumor tissue as well. This newly identified risk score signature based on the combination of 8 miRNAs could significantly predict the prognostic risk of MIBC and might provide insight into immunotherapy and targeted therapy of MIBC.

Highlights

Bladder cancer is a commonly diagnosed malignant tumor arising from the tissues of the urinary system, with around 550,000 new cases and 200,000 deaths being reported worldwide in 2018 [1]
Patients in the the Cancer Genome Atlas (TCGA) dataset were excluded from the present study if they met any of the following criteria: (1) the pathological grade was lower than pT2; (2) the first diagnosis cancer was not bladder cancer; (3) received treatment before being involved in the TCGA cohort; (4) NMIBC patients progressed to muscle-invasive bladder cancer (MIBC) after the tissue was obtained; and (5) the follow-up status and times were not available
In TCGA datasets, a total of 392 patients were included in this study after preprocessing. e demographic and clinical characteristics are listed in Table 1, while in Gene Expression Omnibus (GEO) datasets, a total of 62 patients were included in the present study in which only information on age and survival was available

Summary

Introduction

Bladder cancer is a commonly diagnosed malignant tumor arising from the tissues of the urinary system, with around 550,000 new cases and 200,000 deaths being reported worldwide in 2018 [1]. About 1 out of 4 bladder cancer cases were diagnosed as muscle-invasive bladder cancer (MIBC) when cancer cells have gone through the bladder lining and are present in the detrusor muscle [2, 3]. MIBC has strong invasiveness and is more prone to distal metastasis and recurrence, which brings about a poor 5-year survival of around 50% [4]. Radical cystectomy of the bladder in conjunction with neoadjuvant therapy is still the first-line treatment for MIBC [5]. E 5-year survival rates of MIBC have not improved as much as other cancers during decades [7]. Identifying MIBC prognostic biomarkers at the molecular level will be of great value in distinguishing MIBC cases with different risks, developing individualized clinical therapies, and improving survival rate

Methods

Results

Conclusion