Urine TERT promoter mutations‑based tumor DNA detection in patients with bladder cancer: A pilot study

Abstract

Telomerase reverse transcriptase (TERT) promoter mutations are the most frequent genetic events in bladder cancer (BC). The aim of the present pilot study was to evaluate the diagnostic potential of urine TERT promoter mutations-based liquid biopsy in patients with an ongoing oncological process, as well as in post-resection patients at risk of BC recurrence. A total of 60 patients were enrolled, of whom 27 patients had histologically proven BC; 23 had no signs of BC (control group); and 10 patients underwent transurethral malignancy resection 3-6 months prior to urine donation ('second look' group). Urine TERT promoter mutations were detected using Droplet Digital PCR. Receiver operating characteristic curve analysis revealed significant diagnostic power of the present approach (area under the curve: -0.768). At the cut-off value of tumor DNA fraction 0.34%, the sensitivity and specificity were 55.56 and 100%, respectively. In the positive samples, tumor DNA fraction varied significantly from 0.59 to 48.77%. In the 'second look' group, tumor DNA was detected in 4/10 patients, highlighting the possibility of BC recurrence with its fraction ranging only from 0.90 to 6.61%. Therefore, urine TERT promoter mutations-based liquid biopsy appears to be a promising tool for BC diagnosis and surveillance. The main study will include recruitment of additional patients, extension of the mutation panel, prolonged follow-up of the post-resection patients, as well as screening of industrial workers exposed to specific carcinogens.

A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers

“…In a pilot study [ 49 ] TERT promoter mutations in urine were detected by Droplet Digital PCR. Diagnostic accuracy was evaluated in patients with ongoing oncology and after resection at risk of BCa recurrence.…”

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

“…Such differences in the study populations yield significant differences in a marker’s reported efficacy parameters (i.e., sensitivity, specificity, positive and negative predictive values) of a marker in different studies ( Table 1 ). Therefore, unless a meta-analysis accounts/controls for the different variables across the studies, the reported mean and median efficacies would not be reliable, affecting a marker’s clinical translation [ 200 , 251 , 264 ].…”

“…To counter some of the biases and inaccuracies associated with biomarker studies, the STARD (Standards for Reporting of Diagnostic Accuracy Studies), PRISMA (The Preferred Reporting Items for Systematic reviews and Meta-Analyses), and the updated PRISM-DAT (PRISMA-Diagnostic Accuracy Test) statements/guidelines could be adopted in the meta-analyses and systematic reviews of BC biomarkers [ 264 , 265 , 266 , 267 , 268 ]. Nevertheless, very few biomarker studies for malignant or benign diseases adhere to these guidelines.…”

Diagnostic Performances of Urine Cytology and TERT Promoter Mutations in Bladder Cancer

“…Bladder cancer (BC) is considered the most common urinary tract malignancy, ranking 9 th and 13 th in terms of frequency mortality rates respectively [1]. BC occurrences and mortalities are generally associated in regions with high human development index [2].…”

“…Due to both recent advances in genomic, epigenomic and proteomic studies of tumor fluids, and the development of sensitive analytical molecular techniques, a new approach for cancer detection has emerged, namely liquid biopsy. This technique is based on the analysis of various tumor-related targets circulating in biological fluids, such as blood, urine, saliva and cerebrospinal fluid [1]. These targets include cell-free tumor DNA (tDNA), different types of tumor RNAs, peptides, metabolites, exosomes, endosomes, and even circulating tumor cells [8].…”