Urinary Cell-Free DNA IQGAP3/BMP4 Ratio as a Prognostic Marker for Non–Muscle-Invasive Bladder Cancer

Abstract

Urinary cell-free DNA (ucfDNA) as a liquid biopsy may be a novel noninvasive biomarker for monitoring cancer prognosis. We examined the IQGAP3/BMP4 ratio in ucfDNA from nonemuscle-invasive bladder cancer patients. We observed that high IQGAP3/BMP4 ratio was associated with worse recurrence-free and progression-free survival. Background: Disease monitoring in non–muscle-invasive bladder cancer (NMIBC)patients is crucial for early identification of disease recurrence and progression. High IQGAP3/BMP4 and IQGAP3/FAM107A ratios in urinary cell-free DNA (ucfDNA)are a diagnostic biomarker for bladder cancer. We aimed to investigate whether the levels of these biomarkers in ucfDNA can be used to monitor disease recurrence or progression in patients with NMIBC. Patients and Methods: A total of 103 patients with NMIBC (pTa-pT1)were enrolled. The IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were measured by real-time PCR, and the results were compared with clinical outcome by Kaplan-Meier curves and Cox regression analyses. Results: Overall, 55 patients (53.4%)experienced recurrence and 29 (28.2%)experienced disease progression during a median follow-up of 42.7 months (range, 6.1-172.2 months). Kaplan-Meier analysis revealed that NMIBC patients with a high IQGAP3/BMP4 ratio had worse recurrence-free survival and progression-free survival (PFS)(P =.001 and <.001, respectively), and those with a high IQGAP3/FAM107A ratio had worse PFS (P =.006). Multivariate Cox regression analysis revealed that the IQGAP3/BMP4 ratio was independently associated with recurrence-free survival (hazard ratio, 2.462; P =.003)and PFS (hazard ratio = 3.871; P =.004), whereas the IQGAP3/FAM107A ratio was not an independent factor for PFS (P =.079). Conclusion: The IQGAP3/BMP4 ratio in ucfDNA might be a valuable novel biomarker for predicting disease recurrence and progression in patients with NMIBC. © 2019Urinary cell-free DNA (ucfDNA)as a liquid biopsy may be a novel noninvasive biomarker for monitoring cancer prognosis. We examined the IQGAP3/BMP4 ratio in ucfDNA from non–muscle-invasive bladder cancer patients. We observed that high IQGAP3/BMP4 ratio was associated with worse recurrence-free and progression-free survival. © 2019