Yanjie Xu1, Ye-Hwan Kim2, Pildu Jeong2, Xuan-Mei Piao2, Young Joon Byun2, Ho Won Kang2, Won Tae Kim2, Jong-Young Lee3, Isaac Y Kim4, Sung-Kwon Moon5, Yung Hyun Choi6, Seok Joong Yun2, Wun-Jae Kim7. 1. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea; Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea. 2. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea. 3. Department of Business Data Convergence, Chungbuk National University, Cheongju, Republic of Korea; Theragen Etex Bio Institute, Suwon, Republic of Korea. 4. 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. 5. Department of Food Science and Technology, Chung-Ang University, Ansung, Republic of Korea. 6. Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea. 7. Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea. Electronic address: wjkim@chungbuk.ac.kr.
Abstract
BACKGROUND: Urinary cell-free DNA (ucfDNA) has great potential as a "liquid biopsy" for use in diagnosis of urological cancers. In this study, we compared ucfDNA gene expression levels between patients with bladder cancer (BC) and those with hematuria, and determined whether they could be used as a noninvasive urine-based marker. METHODS: The study cohort of 355 patients included a screening group (40 BC and 41 hematuria controls) and a validation cohort (149 BC and 125 hematuria controls). Expression levels ratios of 1 up-regulated gene (IQGAP3) to those of 7 down-regulated genes were examined in ucfDNA in the screening group to identify ratios that differed significantly between BC and hematuria patients. IQGAP3/BMP4 and IQGAP3/FAM107A ratios were selected and combined to develop a discriminant score (DS) index, which was tested in the validation cohort. Receiver operating characteristic curves and areas under the curve were calculated to evaluate the performance of the DS index. RESULTS: IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were both significantly higher in BC patients than in hematuria patients (both P < 0.001). The DS index had an area under the curve of 0.862, a sensitivity of 71.0%, a specificity of 88.6%, a positive predictive value of 90.3%, and a negative predictive value of 67.2%. CONCLUSIONS: Both IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were significantly higher in patients with BC than in those with hematuria. The DS index exhibits good diagnostic performance as a noninvasive biomarker.
BACKGROUND: Urinary cell-free DNA (ucfDNA) has great potential as a "liquid biopsy" for use in diagnosis of urological cancers. In this study, we compared ucfDNA gene expression levels between patients with bladder cancer (BC) and those with hematuria, and determined whether they could be used as a noninvasive urine-based marker. METHODS: The study cohort of 355 patients included a screening group (40 BC and 41 hematuria controls) and a validation cohort (149 BC and 125 hematuria controls). Expression levels ratios of 1 up-regulated gene (IQGAP3) to those of 7 down-regulated genes were examined in ucfDNA in the screening group to identify ratios that differed significantly between BC and hematuriapatients. IQGAP3/BMP4 and IQGAP3/FAM107A ratios were selected and combined to develop a discriminant score (DS) index, which was tested in the validation cohort. Receiver operating characteristic curves and areas under the curve were calculated to evaluate the performance of the DS index. RESULTS:IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were both significantly higher in BC patients than in hematuriapatients (both P < 0.001). The DS index had an area under the curve of 0.862, a sensitivity of 71.0%, a specificity of 88.6%, a positive predictive value of 90.3%, and a negative predictive value of 67.2%. CONCLUSIONS: Both IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were significantly higher in patients with BC than in those with hematuria. The DS index exhibits good diagnostic performance as a noninvasive biomarker.