Yanjie Xu1, Ye-Hwan Kim2, Pildu Jeong2, Xuan-Mei Piao2, Young Joon Byun2, Sung Pil Seo2, Ho Won Kang2, Won Tae Kim2, Jong-Young Lee3, Dong Hee Ryu4, Jae-Woon Choi4, Isaac Y Kim5, Sung-Kwon Moon6, Yung Hyun Choi7, Seok Joong Yun2, Wun-Jae Kim8. 1. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea; Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea. 2. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea. 3. Department of Business Data Convergence, Chungbuk National University, Cheongju, Korea; Theragen Etex Bio Institute, Suwon, Korea. 4. Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea. 5. Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ. 6. Department of Food Science and Technology, Chung-Ang University, Ansung, Korea. 7. Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Korea. 8. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Korea. Electronic address: wjkim@chungbuk.ac.kr.
Abstract
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.
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.