Diagnostic Potential of Circulating Tumor Cells, Urinary MicroRNA, and Urinary Cell-Free DNA for Bladder Cancer: A Review

Abstract

Early detection of primary bladder cancer (BCa) is vital, because stage and grade have been generally accepted not only as categorical but also as prognostic factors in patients with BCa. The widely accepted screening methods for BCa, cystoscopy and urine cytology, have unsatisfactory diagnostic accuracy, with high rates of false negatives, especially for flat-type BCa with cystoscopy and for low-risk disease with urine cytology. Currently, liquid biopsy has attracted much attention as being compensatory for that limited diagnostic power. In this review, we survey the literature on liquid biopsy for the detection of BCa, focusing on circulating tumor cells (CTCs), urinary cell-free DNA (ucfDNA), and urinary microRNA (umiRNA). In diagnostic terms, CTCs and umiRNA are determined by quantitative analysis, and ucfDNA relies on finding genetic and epigenetic changes. The ideal biomarkers should be highly sensitive in detecting BCa. Currently, CTCs produce an unfavorable result; however, umiRNA and ucfDNA, especially when analyzed using a panel of genes, produce promising results. However, given the small cohort size in most studies, no conclusions can yet be drawn about liquid biopsy’s immediate application to clinical practice. Further large studies to validate the diagnostic value of liquid biopsy for clinical use are mandatory.

Recent development of urinary biomarkers for bladder cancer diagnosis and monitoring

“…ucfDNAs also gain attention due to their close contact with lesions of urinary disease and are therefore considered potential urine biomarkers for BC. 26,27 Recent clinical research found that ucfDNA can monitor the recurrence and progression of NMIBC. Xu et al 28 enrolled 103 patients with NMIBC (pTa-pT1) and measured the IQGAP3/BMP4 expression ratios in ucfDNA by real-time quantitative polymerase chain reaction (RT-qPCR).…”

“…Currently, plasma cfDNA is widely explored for its potential in tumour detection. ucfDNAs also gain attention due to their close contact with lesions of urinary disease and are therefore considered potential urine biomarkers for BC 26,27 . Recent clinical research found that ucfDNA can monitor the recurrence and progression of NMIBC.…”

Blood-based liquid biopsy: insights into early detection, prediction, and treatment monitoring of bladder cancer

“…Liquid biopsy is based on the detection of circulating tumor cells (CTCs) and “cell-free” nucleic acids in blood and body fluids, including urine, saliva, tears, sweat, amniotic fluid, cerebrospinal and pleural fluids, and cervicovaginal secretions, to detect and quantify targets of interest [ 13 , 14 ]. Significant progress has been made in the detection of urinary biomarkers for BC, but it is currently limited by its low sensitivity and specificity [ 15 , 16 ]. Since blood is in contact with most tumors, liquid biopsies mainly involve blood sampling.…”

Urinary miRNAs as a Diagnostic Tool for Bladder Cancer: A Systematic Review

“…Although the alteration of miRNAs has not been fully elucidated in the bladder, miRNAs are deregulated in bladder cancer and have been seen to promote cell proliferation and progression through epithelial-to-mesenchymal transition and inhibit apoptosis [ 15 , 16 ]. Therefore, thanks to their high stability in biological fluids, miRNAs represent one of the most promising biomarkers for cancer detection, including bladder cancer [ 17 ]. Here, we provide a systematic overview to collect and summarize the current state-of-the-art trials on urine miRNAs as promising biomarkers for a BC diagnosis.…”