Abstract

Currently, voided urine cytology (VUC) serves as the gold standard for the detection of bladder cancer (BCa) in urine. Despite its high specificity, VUC has shortcomings in terms of sensitivity. Therefore, alternative biomarkers are being searched, which might overcome these disadvantages as a useful adjunct to VUC. The aim of this study was to evaluate the diagnostic potential of the urinary levels of selected microRNAs (miRs), which might represent such alternative biomarkers due to their BCa-specific expression. Expression levels of nine BCa-associated microRNAs (miR-21, -96, -125b, -126, -145, -183, -205, -210, -221) were assessed by quantitative PCR in urine sediments from 104 patients with primary BCa and 46 control subjects. Receiver operating characteristic (ROC) curve analyses revealed a diagnostic potential for miR-96, -125b, -126, -145, -183, and -221 with area under the curve (AUC) values between 0.605 and 0.772. The combination of the four best candidates resulted in sensitivity, specificity, positive and negative predictive values (NPV), and accuracy of 73.1%, 95.7%, 97.4%, 61.1%, and 80.0%, respectively. Combined with VUC, sensitivity and NPV could be increased by nearly 8%, each surpassing the performance of VUC alone. The present findings suggested a diagnostic potential of miR-125b, -145, -183, and -221 in combination with VUC for non-invasive detection of BCa in urine.

Highlights

  • Bladder cancer (BCa) was the 10th most common malignancy worldwide with 550,000 new cases and an estimated 200,000 deaths in 2018 [1,2]

  • Patients with non-muscle-invasive BCa (NMIBC; pTa and pT1) and concomitant pTis were allocated to the pTis group (10 of the 15 pTis cases; 9.6% of all BCa)

  • The remaining five patients with muscle-invasive BCa (MIBC) and concomitant pTis were allocated to the group ≥pT2, resulting in a total of 22 patients with MIBC with or without concomitant pTis (21.1% of all BCa)

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Summary

Introduction

Bladder cancer (BCa) was the 10th most common malignancy worldwide with 550,000 new cases and an estimated 200,000 deaths in 2018 [1,2]. In men, who are four times more frequently affected than women, BCa ranks sixth of all newly diagnosed cancers and is the ninth most deadly cancer worldwide [2]. Tissue specimens obtained during transurethral resection of the bladder (TUR-B) undergo histopathological examination for assessment of the putative tumor grade and stage [3]. The same approach is used for regular follow-up after treatment to detect BCa recurrence and progression. Among other factors, these life-long, frequent, and cost-intensive surveillance procedures make BCa one of the most expensive tumor entities [4,5]

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