Value of urinary topoisomerase-IIA cell-free DNA for diagnosis of bladder cancer

Abstract

PurposeTopoisomerase-II alpha (TopoIIA ), a DNA gyrase isoform that plays an important role in the cell cycle, is present in normal tissues and various human cancers, and can show altered expression in both. The aim of the current study was to examine the value of urinary TopoIIA cell-free DNA as a noninvasive diagnosis of bladder cancer (BC).Materials and MethodsTwo patient cohorts were examined. Cohort 1 (73 BC patients and seven controls) provided bladder tissue samples, whereas cohort 2 (83 BC patients, 54 nonmalignant hematuric patients, and 61 normal controls) provided urine samples. Real-time quantitative polymerase chain reaction was used to measure expression of TopoIIA mRNA in tissues and TopoIIA cell-free DNA in urine samples.ResultsThe results showed that expression of TopoIIA mRNA in BC tissues was significantly higher than that in noncancer control tissues (p<0.001). The expression of urinary TopoIIA cell-free DNA in BC patients was also significantly higher than that in noncancer patient controls and hematuria patients (p < 0.001 and p < 0.001, respectively). High expression of urinary TopoIIA cell-free DNA was also detected in muscle invasive bladder cancer (MIBC) when compared with nonmuscle invasive bladder cancer (NMIBC) (p=0.002). Receiver operating characteristics (ROC) curve analysis was performed to examine the sensitivity/specificity of urinary TopoIIA cell-free DNA for diagnosing BC, NMIBC, and MIBC. The areas under the ROC curve for BC, NMIBC, and MIBC were 0.741, 0.701, and 0.838, respectively.ConclusionsIn summary, the results of this study provide evidence that cell-free TopoIIA DNA may be a potential biomarker for BC.

New method to preserve the original proportion and integrity of urinary cell‐free DNA

“…To mitigate this problem, some researchers have added EDTA or EDTA‐K 3 solution to urine samples to inhibit nuclease activity . Other precautions such as using a sterile container to collect urine and keeping urine samples at 4°C or on ice to reduce nuclease activity. Unfortunately, these procedures make urine collection and transport inconvenient and may threaten the stability of the ucfDNA.…”

Biomarkers for bladder cancer: The search continues!

“…Research accomplished so far has taught us that noninvasive urinary markers are not limited to use in bladder cancer detection. Findings from the current study by Kim et al [ 1 ] provide us with hope that discovery of such a marker is nearing. As the effort continues to replace prostate biopsy, which certainly is an uncomfortable experience for many patients, in the diagnosis of prostate cancer, the same should be done to spare patients the agony of cystoscopy.…”

“…In this issue of Investigative and Clinical Urology , findings are reported from an elegant study by Kim et al [ 1 ] on the value of urinary topoisomerase-II alpha ( TopoIIA ) cell-free DNA for diagnosis of bladder cancer. In this study, Kim et al [ 1 ] observed significantly higher expression of urinary TopoIIA cell-free DNA in bladder cancer patients compared with controls and nonmalignant hematuria patients. Also, expression of urinary TopoIIA cell-free DNA was revealed to be significantly higher in patients with muscle-invasive bladder cancer than in those with non–muscle-invasive bladder cancer in this study.…”

Emerging Biomarkers in Bladder Cancer Identified by Network Analysis of Transcriptomic Data

“…Serum concentration of TK1 (Thymidine kinase 1) gene was associated with tumor stage, degree of invasion, and metastasis ( 32 ). TOP2A (Topoisomerase-IIA) free DNA in urine has been identified as a diagnostic biomarker and its levels can also distinguish NMIBC from MIBC ( 33 ). Its over-expression has also been associated with high-grade and high-stage BCa and with high rates of recurrence in NMIBC ( 34 ).…”