Abstract
Bladder cancer (BC) is among the most frequent malignancies worldwide, being the most expensive cancer to treat and monitor and the most lethal urological cancer. Urine microRNAs (miRNAs) have been proposed as novel non-invasive biomarkers to early diagnose and monitor BC patients in order to avoid the performance of current aggressive diagnostic techniques. However, huge discrepancies arise among studies mainly due to the lack of standardization in the normalization, a crucial step in all miRNA studies. Our aim was to identify the best miRNA normalizer for miRNA studies in urine of BC patients. We evaluated the performance of 110 candidate miRNAs in urine of 35 BC patients and 15 healthy controls by Real Time quantitative Polymerase Chain Reaction (RT-qPCR) followed by a stability analysis with RefFinder. In this screening stage, miR-29c-3p arose as the most stably expressed miRNA in BC and controls, with a good expression level. Stability of miR-29c-3p expression was validated in an independent cohort of 153 BC patients and 57 controls. Finally, we evaluated the robustness of miR-29c-3p as normalizer in the expression study of miR-200c-3p, a potential diagnostic marker for BC. We propose miR-29c-3p as a normalizer for miRNA studies in BC urine. This is the first study that characterizes a reliable normalizer that may allow the comparison of future urine miRNA studies as non-invasive biomarkers for BC diagnosis and monitoring.
Highlights
Bladder cancer (BC) is among the most frequent malignancies worldwide
BestKeeper were selected by any other algorithm, none of them were included in the comprehensive ranking provided by RefFinder and discarded as potential normalizers in our study
Expression levels, an accurate data analysis ought to be performed using appropriate normalizers for external and internal variation correction [26]. These normalizers should be chosen from a selection of candidates that are expected to be stably expressed over the entire range of samples being investigated, since miRNAs can be affected by the condition under study
Summary
Bladder cancer (BC) is among the most frequent malignancies worldwide. According to the GLOBOCAN 2018 study, BC accounts for more than 540,000 new cases worldwide and almost. BC largely increases health expenses since it is the most expensive cancer to treat and the one that accounts for the highest monitoring costs. The cost of the muscle-invasive subtype reaches $150,000 per capita [3,4] and, by the end of the decade, BC is expected to account for >3% of all cancer-related medical expenses [3]. Bladder ultrasound, computerized tomography (CT) scan, cystoscopy or cytology are presently the gold standard techniques for BC diagnosis. Cystoscopy is a highly invasive procedure that causes a high discomfort in patients and urine cytology, while being non-invasive, is unable
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