Research Papers:

Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer

Won Tae Kim, Ye Hwan Kim, Pildu Jeong, Sung-Pil Seo, Ho-Won Kang, Yong-June Kim, Seok Joong Yun, Sang-Cheol Lee, Sung-Kwon Moon, Yung-Hyun Choi, Geun Taek Lee, Isaac Yi Kim and Wun-Jae Kim _

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Oncotarget. 2018; 9:14354-14365. https://doi.org/10.18632/oncotarget.24436

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Won Tae Kim1,2,5,*, Ye Hwan Kim1,*, Pildu Jeong1, Sung-Pil Seo1,2, Ho-Won Kang1,2, Yong-June Kim1,2, Seok Joong Yun1,2, Sang-Cheol Lee1,2, Sung-Kwon Moon3, Yung-Hyun Choi4, Geun Taek Lee5, Isaac Yi Kim5 and Wun-Jae Kim1,2

1Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea

2Department of Urology, Chungbuk National University Hospital, Cheongju, Chungbuk, South Korea

3School of Food Science and Technology, Chung-Ang University, Anseong, South Korea

4Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, South Korea

5Section of Urological Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

*These authors have contributed equally to this work

Correspondence to:

Wun-Jae Kim, email: [email protected]

Isaac Yi Kim, email: [email protected]

Keywords: biomarkers; nucleic acids; urinary bladder neoplasms; urine

Received: April 26, 2017    Accepted: July 12, 2017    Epub: February 07, 2018    Published: March 06, 2018


Background: There is growing interest in developing new non-invasive diagnostic tools for bladder cancer (BC) that have better sensitivity and specificity than cystoscopy and cytology. This study examined the value of urinary cell-free nucleic acid (NA) as a diagnostic marker for BC.

Material and methods: A total of 81 patients (74 BC and 7 normal controls) were used for a tissue set, and 212 patients (92 BC and 120 normal controls) were used as a urine set. Expression of tissue mRNA and urinary cell-free NAs was then examined.

Results: Four candidate genes were top-ranked in the tissue microarray. Expression levels of two of these (IQGAP3 and TOP2A) in BC tissue and urine samples from BC patients were significantly higher than those in samples from the control groups. Binary logistic regression analysis of cell-free NA levels in urine samples revealed that IQGAP3 was significantly associated with BC: PicoGreen-adjusted odds ratio (OR), 3.434; confidence interval (CI), 2.999–4.180; P<0.001; RiboGreen-adjusted OR, 2.242; CI, 1.793–2.840; P<0.001. Further analysis of IQGAP3 urinary cell-free NAs with respect to tumor invasiveness and grade also yielded a high AUC, suggesting that IQGAP3 can discriminate between BC patients and non-cancer patients with hematuria.

Conclusions: Levels of IQGAP3 urinary cell-free NA in BC patients were significantly higher than those in normal controls or patients with hematuria. High levels of IQGAP3 urinary cell-free NA also reflected high expression in BC tissues. Therefore, IQGAP3 urinary cell-free NA may be a complementary diagnostic biomarker for BC.

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