Urinary Exosomal miRNAs Can Be Utilized as Biomarkers to Detect Early and Invasive Bladder Cancer

Abstract

Bladder cancer (BC) accounts for over 500,000 cases diagnosed yearly worldwide and about 83,700 new cases diagnosed in USA in 2021. It is estimated that 17,200 patients will die each year in the USA, due to high rates of tumor recurrence and cancer progression. In early stages, (noninvasive), BC is associated with a favorable course, but 20% of the cases are aggressive and have dismal prognosis[1]. The purpose of our study is to identify biomarkers that will help in the diagnosis of the disease in early stages to improve survival. Exosomes are extracellular vesicles that bud off the cell membrane that can be secreted in most body fluids including blood, urine and CSF. Exosomes carry markers of the secretory cells of origin, including those of endosome origin, those involved in intracellular transport, those of cell membrane origin as well as RNA and double stranded DNAs. MicroRNA contained within the exosome has been implicated in modulating recipient cell functions. Tumor cells release exosomes into the extracellular space which has led to increased use of liquid biopsy to identify biomarkers that can aid in early detection of cancer[2]. We studied exosomal miRNA expression from urine samples in patients with BC to evaluate their possible role as tumor markers. Urine samples were collected from 14 patients with BC at different stages seen in a protocol approved, at the UOB in the NIH. Exosomal RNAs isolated from urine samples were extracted and quantified. RNA was amplified for miRNA expression profile using 384-SeraMir profile qPCR array. Significant and highly expressed microRNAs were selected for analysis. MicroRNAs commonly dysregulated in urine BC samples were: has-125b-5p, hsa-Let-7b, hsa-148a-5p, hsa- 30da-5p, hsa-423-5p, hsa-16-5p and hsa-191-5p. MicroRNA profiles from the urine samples will be matched with the tumor tissues in each case. From the total of MicroRNAs obtained, 274 were known microRNAs and 334 were novel predicted microRNAs. Our study demonstrates the potential of exosomal microRNAs as a useful biomarker to detect non- and invasive bladder cancer. The biomarkers have great potential not only for diagnosis, but also for early detection, detection of tumor recurrence and progression, and treatment response.