Abstract

BackgroundThis study aimed to construct prognostic model by screening prognostic miRNA signature of bladder cancer.MethodsThe miRNA expression profile data of bladder cancer (BC) in The Cancer Genome Atlas (TCGA) were obtained and randomly divided into the training set and the validation set. Differentially expressed miRNAs (DEMs) between BC and normal control samples in the training set were firstly identified, and DEMs related to prognosis were screened by Cox Regression analysis. Then, the MiR Score system was constructed using X-Tile based cutoff points and verified in the validation set. The prognostic clinical factors are selected out by univariate and multivariate Cox Regression analysis. Finally, the mRNAs related to prognosis were screened and the biological pathway analysis was carried out.ResultsWe identified the 7-miRNA signature was significantly associated with the patient’s Overall Survival (OS). A prognostic model was constructed based on the prognostic 7-miRNA signature, and possessed a relative satisfying predicted ability both in the training set and validation set. In addition, univariate and multivariate Cox Regression analysis showed that age, lymphovascular invasion and MiR Score were considered as independent prognostic factors in BC patients. Furthermore, based on MiR Score prognostic model, several differentially expressed genes (DEGs), such as WISP3 and UNC5C, as well as their related biological pathway(s), including cell–cell adhesion and neuroactive ligand-receptor interaction, were considered to be related to BC prognosis.ConclusionThe prognostic model which was constructed based on the prognostic 7-miRNA signature presented a high predictive ability for BC.

Highlights

  • This study aimed to construct prognostic model by screening prognostic miRNA signature of bladder cancer

  • The independent prognostic factors analysis Univariate and multivariate Cox Regression analysis showed that age > 65 years [hazard ratio = 1.016, 95% confidence interval (CI) 1.011–1.430, p = 2.034 × 10−2 and HR = 1.069, 95% CI 1.0262–1.113, p = 1.340 × 10−3], lymphovascular invasion (HR = 1.709, 95% CI 0.893– 3.274, p = 1.050 × 10−2 and HR = 1.338, 95% CI 1.056– 3.177, p = 4.509 × 10−2) and MiR miRNA prognosis score (Score)

  • This study found that several differentially expressed genes (DEGs), such as WISP3 and UNC5C, were closely associated with Bladder cancer (BC) prognosis

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Summary

Introduction

This study aimed to construct prognostic model by screening prognostic miRNA signature of bladder cancer. Bladder cancer (BC) is one of the most common malignant tumor of the urinary system, which is characterized by the high rate of non-muscle invasive BC (NMIBC) at the moment of diagnosis (75–80%) [1, 2], with approximately 3.4 million affected cases and 188,000 deaths in. The standard BC screening methods include cystoscopy, sonography, and urinary cytology; its high invasiveness and low accuracy still cannot be neglected [4]. Radical cystectomy (RC) is usually performed in patients with early diagnosis of muscular invasive cystitis (MIBC). This is not the best solution because patients have a poor quality of life after. It is important to further reveal novel diagnostic and therapeutic methods, as well as underlying risk factors for poor prognosis of BC patients

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