Universität zu Köln

Hayashi, Yujiro, Fujita, Kazutoshi ORCID: 0000-0002-6774-7497, Matsuzaki, Kyosuke, Eich, Marie-Lisa, Tomiyama, Eisuke, Matsushita, Makoto, Koh, Yoko, Nakano, Kosuke, Wang, Cong, Ishizuya, Yu, Kato, Taigo, Hatano, Koji, Kawashima, Atsunari, Ujike, Takeshi, Uemura, Motohide, Imamura, Ryoichi, Netto, George J. and Nonomura, Norio (2020). Clinical Significance of Hotspot Mutation Analysis of Urinary Cell-Free DNA in Urothelial Bladder Cancer. Front. Oncol., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

Recent studies showed the clinical utility of next-generation sequencing of urinary cell-free DNA (cfDNA) from patients with urothelial bladder cancer (UBC). In this study, we aimed to develop urinary cfDNA analysis by droplet digital PCR (ddPCR) as a high-throughput and rapid assay for UBC detection and prognosis. We analyzed urinary cfDNA of 202 samples from 2 cohorts. Test cohort was designed for investigating clinical utility of urinary cfDNA, and was composed of 74 samples from patients with UBC, and 52 samples of benign hematuria patients. Validation cohort was designed for validation and assessment of clinical utility comparing urinary cfDNA with UroVysion (Abbott, Illinois, USA), and was composed of 40 samples from patients with UBC, and 36 prospectively collected samples from patients under surveillance after surgery for urothelial carcinoma. We performed ddPCR analysis of hotspot gene mutations (TERT promoter and FGFR3). In the test cohort, the sensitivity of urinary cfDNA diagnosis was 68.9% (51/74) and the specificity was 100% in patients with UBC. The sensitivity increased to 85.9% when used in conjunction with urine cytology. In addition, patients with high TERT C228T allele frequency (>= 14%) had significantly worse prognosis in bladder tumor recurrence than patients with low TERT C228T allele frequency or negative TERT C228T (p = 0.0322). In the validation cohort, the sensitivity of urinary cfDNA was 57.5% (23/40) and the specificity was 100% in UBC patients. The sensitivity of the combination of urine cytology with our hotspot analysis (77.5%) was higher than that of urine cytology with UroVysion (68.9%). In the post-surgical surveillance group, patients positive for the TERT C228T mutation had significantly worse prognosis for bladder tumor recurrence than mutation negative patients (p < 0.001). In conclusion, ddPCR analysis of urinary cfDNA is a simple and promising assay for the clinical setting, surpassing UroVysion for detection and prognosis determination in UBC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hayashi, Yujiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Fujita, Kazutoshi UNSPECIFIED orcid.org/0000-0002-6774-7497 UNSPECIFIED Matsuzaki, Kyosuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Eich, Marie-Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Tomiyama, Eisuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Matsushita, Makoto UNSPECIFIED UNSPECIFIED UNSPECIFIED Koh, Yoko UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakano, Kosuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Cong UNSPECIFIED UNSPECIFIED UNSPECIFIED Ishizuya, Yu UNSPECIFIED UNSPECIFIED UNSPECIFIED Kato, Taigo UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatano, Koji UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawashima, Atsunari UNSPECIFIED UNSPECIFIED UNSPECIFIED Ujike, Takeshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Uemura, Motohide UNSPECIFIED UNSPECIFIED UNSPECIFIED Imamura, Ryoichi UNSPECIFIED UNSPECIFIED UNSPECIFIED Netto, George J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nonomura, Norio UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-333381
DOI:	10.3389/fonc.2020.00755
Journal or Publication Title:	Front. Oncol.
Volume:	10
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2234-943X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TERT PROMOTER MUTATIONS; SITU HYBRIDIZATION ASSAY; TUMOR MARKERS; CARCINOMA; CYTOLOGY; SURVEILLANCE; BIOMARKERS; RECURRENCE; CHROMATIN; PANEL Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33338