Abstract 2604: Urinary microRNAs as biomarkers for early detection of urothelial cancer

Abstract

microRNAs modulate gene expression in various cancer types, and their profiles differ in healthy and cancer groups of people and they represent a warning sign for various cancer scenarios. Identification of tumor-specific microRNAs presents a powerful opportunity to potentially reduce cancer mortality through early detection. In order to achieve early detection through population screening, noninvasive approaches are needed to complement and improve upon current strategies for urothelial cancer (UC) screening. Since all microRNAs in the blood cannot be transferred from donor to recipient cells during single blood circulation, kidney filtration could pass some untransferred microRNAs from blood to urine, therefore urinary microRNAs might be used as biomarkers for the diagnosis of cancer. We investigated whether urine levels of microRNA can differentiate patients with UC from healthy individuals. Here, we successfully identified UC-related microRNA ensembles in urine through a combination of microfluidic microRNA extraction device and machine learning-based analysis. We analyzed 93 urine samples from 27 UC patients and 66 healthy individuals (controls). An initial set of 74 microRNAs was selected by microarray microRNA profiling assay as biomarker candidates. Quantitative reverse-transcription PCR was used for further analysis to validate the expression of microRNAs. We selected a group of 6 microRNAs for validation; (miR-6089, miR-4488, miR-4784, miR-26a-5p, miR-148a-3p, and miR-143-3p) were confirmed to be significantly different in UC and controls. We adopted a logistic regression model and successfully developed a classifier based on these 6 microRNAs, which showed remarkably high sensitivity (94%) and specificity (85%). In summary, patients with UC have significantly different patterns of microRNA expression from healthy individuals. We identified a signature of 6 microRNAs as predictors that can differentiate patients with UC from those who are healthy. These microRNAs could be potentially developed as biomarkers for UC. Citation Format: Kazuya Takayama, Kohei Yamazaki, Hiroki Yamaguchi, Keishu Tsuda, Takao Yasui, Yuki Ichikawa. Urinary microRNAs as biomarkers for early detection of urothelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2604.