Expanding frontiers in liquid biopsy-discovery and validation of circulating biomarkers in renal cell carcinoma and bladder cancer.

Renal cell carcinoma (RCC) and Bladder cancer (BC) are two lethal urological cancers that require diagnosis at their earliest stage causing decreasing survival rates in case of aggressive disease. However, there is no reliable circulating marker in blood or urine for their less or non-invasive diagnosis. Our objective was to review the potential circulating biomarkers, namely proteins, micro-RNA (miRNA), long non-coding RNA (lncRNA), and circulating tumour cells (CTCs) for which we performed a PubMed-based literature search of biomolecules (protein, miRNA, lncRNA and CTCs) found as circulating biomarkers in blood and urine for the early detection of RCC and BC. Among the numerous studies, certain biomolecules represent promising early-stage biomarkers such as proteins (NNMT, LCP1, and NM23A; KIM1), mi-RNAs (5-panel: miR-193a-3p, miR-362, miR-572, miR-378, and miR-28-5p; miR-200a) and lncRNAs (5-panel: LET, PVT1, PANDAR, PTENP1 and linc00963; GIHCG) for RCC. Similarly, proteins (APOA1), miRNAs (7-panel: miR-7-5p, miR-22-3p, miR-29a-3p, miR-126-5p, miR- 200a-3p, miR-375, and miR-423-5p; miRNA 181a, miRNA 30c, and miRNA 570) and lncRNAs (3-panel: MALAT1, MEG3, and SNHG16; exosomal derived 3-panel: PCAT-1, UBC1 and SNHG16; H19) were reported in BC subjects. Notably, the majority of the biomarkers presented for early detection in RCC cases were found in blood, while in urine for BC. Our results reveal that though a plethora of circulating biomarkers show early diagnostic ability, all of them are still bench-only biomarkers and require further validation. Adequate clinical trials/studies testing which of these potential markers individually or in combination, will become clinically applicable still remain elusive.