Abstract
Simple SummaryUrothelial carcinoma (UC) is the most frequently diagnosed cancer of the urinary tract and is ranked the sixth most diagnosed cancer in men worldwide. About 70–75% of newly diagnosed UCs are non-invasive or low grade. Different tests such as urine cytology and cystoscopy are used to detect UC. If abnormal tissue is found during cystoscopy, then a biopsy will be performed. Cytology has low sensitivity for low-grade cancer while cystoscopy is invasive and costly. Detecting UC early improves the chances of treatment success. Therefore, many researchers have painstakingly identified urine biological markers for non-invasive UC diagnosis. In this review, we summarize some of the latest and most promising biological markers (including FDA-approved and investigational markers). We also discuss some new technologies that can aid research efforts in biological marker discovery for early UC detection.Urothelial carcinoma (UC) is the most frequent malignancy of the urinary system and is ranked the sixth most diagnosed cancer in men worldwide. Around 70–75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer (NMIBC) subtype, which can be treated by a transurethral resection of the tumor. However, patients require life-long monitoring due to its high rate of recurrence. The current gold standard for UC diagnosis, prognosis, and disease surveillance relies on a combination of cytology and cystoscopy, which is invasive, costly, and associated with comorbidities. Hence, there is considerable interest in the development of highly specific and sensitive urinary biomarkers for the non-invasive early detection of UC. In this review, we assess the performance of current diagnostic assays for UC and highlight some of the most promising biomarkers investigated to date. We also highlight some of the recent advances in single-cell technologies that may offer a paradigm shift in the field of UC biomarker discovery and precision diagnostics.
Highlights
Bladder cancer (BC) is among the top 10 most common types of cancer worldwide, with around 550,000 new cases annually [1], and confers the highest financial burden to developed countries
Cytokeratins are components of cytoplasmic intermediate filaments found in epithelial cells; cytokeratin 20 (CK-20) is expressed in urothelial carcinoma but not normal urothelial cells
Urinary biomarkers are attractive because the testing is non-invasive and cost-efficient, and the sample collection is easy compared to the invasive cystoscopy gold standard tests
Summary
Bladder cancer (BC) is among the top 10 most common types of cancer worldwide, with around 550,000 new cases annually [1], and confers the highest financial burden to developed countries. Urine cytology is inexpensive and commonly used for initial detection of malignant cells, whereas cystoscopy with biopsy confirms the presence of the tumor [4] and allows for pathologic staging. The development of novel non-invasive urinary tests to detect UC-specific biomarkers has increased over the last few decades [6,7,8]. Both soluble and cell-based, aims to detect either exfoliated tumor cells, protein or DNA/RNA changes in urine samples. Some Most of the promising investigational urinary biomarkers for UC andaims their sensitivity/specificity shown and tumor combiomarkers, both soluble and cell-based, to detect eitherare exfoliated cells, protein or pared against the FDA-approved in-vitro diagnostic (IVD) tests. Their sensitivity/specificity are shown and compared against the FDA-approved in-vitro diagnostic (IVD) tests.
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