Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria

Yanjie Xu, Ye Hwan Kim, Pildu Jeong, Xuan Mei Piao, Young Joon Byun, Ho Won Kang, Won Tae Kim, Jong Young Lee, Isaac Kim, Sung Kwon Moon, Yung Hyun Choi, Seok Joong Yun, Wun Jae Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalUrologic Oncology: Seminars and Original Investigations
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Hematuria
Urinary Bladder Neoplasms
DNA
Area Under Curve
Urologic Neoplasms
ROC Curve
Genes
Cohort Studies
Biomarkers
Urine
Biopsy
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Cite this

Xu, Yanjie ; Kim, Ye Hwan ; Jeong, Pildu ; Piao, Xuan Mei ; Byun, Young Joon ; Kang, Ho Won ; Kim, Won Tae ; Lee, Jong Young ; Kim, Isaac ; Moon, Sung Kwon ; Choi, Yung Hyun ; Yun, Seok Joong ; Kim, Wun Jae. / Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria. In: Urologic Oncology: Seminars and Original Investigations. 2019 ; Vol. 37, No. 1. pp. 86-96.
@article{3e85248167a2401d8088a821b554bc68,
title = "Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria",
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.",
author = "Yanjie Xu and Kim, {Ye Hwan} and Pildu Jeong and Piao, {Xuan Mei} and Byun, {Young Joon} and Kang, {Ho Won} and Kim, {Won Tae} and Lee, {Jong Young} and Isaac Kim and Moon, {Sung Kwon} and Choi, {Yung Hyun} and Yun, {Seok Joong} and Kim, {Wun Jae}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.urolonc.2018.10.023",
language = "English (US)",
volume = "37",
pages = "86--96",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "1",

}

Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria. / Xu, Yanjie; Kim, Ye Hwan; Jeong, Pildu; Piao, Xuan Mei; Byun, Young Joon; Kang, Ho Won; Kim, Won Tae; Lee, Jong Young; Kim, Isaac; Moon, Sung Kwon; Choi, Yung Hyun; Yun, Seok Joong; Kim, Wun Jae.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 37, No. 1, 01.01.2019, p. 86-96.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria

AU - Xu, Yanjie

AU - Kim, Ye Hwan

AU - Jeong, Pildu

AU - Piao, Xuan Mei

AU - Byun, Young Joon

AU - Kang, Ho Won

AU - Kim, Won Tae

AU - Lee, Jong Young

AU - Kim, Isaac

AU - Moon, Sung Kwon

AU - Choi, Yung Hyun

AU - Yun, Seok Joong

AU - Kim, Wun Jae

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056383474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056383474&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2018.10.023

DO - 10.1016/j.urolonc.2018.10.023

M3 - Article

VL - 37

SP - 86

EP - 96

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

IS - 1

ER -