Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer

Author:

Miyake Makito1ORCID,Nishimura Nobutaka1,Ohnishi Sayuri1,Oda Yuki1,Owari Takuya1,Ohnishi Kenta1,Morizawa Yosuke1ORCID,Hori Shunta1,Gotoh Daisuke1ORCID,Nakai Yasushi1,Torimoto Kazumasa1,Fujii Tomomi2ORCID,Tanaka Nobumichi13,Fujimoto Kiyohide1ORCID

Affiliation:

1. Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan

2. Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan

3. Department of Prostate Brachytherapy, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan

Abstract

The clinical utility of urine nectins in bladder cancer (BCa) is unclear. We investigated the potential diagnostic and prognostic values of urine Nectin-2 and Nectin-4. Levels of urine Nectin-2, Nectin-4, and NMP-22 were quantified using an enzyme-linked immunosorbent assay in 122 patients with BCa, consisting of 78 with non-muscle-invasive BCa (NMIBC) and 44 with muscle-invasive BCa (MIBC), and ten healthy controls. Tumor nectin expression in MIBC was evaluated with immunohistochemical staining of transurethral resection specimens. The level of urine Nectin-4 (mean: 18.3 ng/mL) was much higher than that of urine Nectin-2 (mean: 0.40 ng/mL). The sensitivities of Nectin-2, Nectin-4, NMP-22, and cytology assays were 84%, 98%, 52%, and 47%, respectively; their specificities were 40%, 80%, 100%, and 100%, respectively. Both urine Nectin-2 and Nectin-4, though not NMP-22, were found to be significantly more sensitive than cytology. A four-titer grouping based on levels of urine Nectin-2/Nectin-4 (low/high, high/high, low/low, and high/low) showed a high capability for discriminating between NMIBC and MIBC. Neither urine Nectin-2 nor Nectin-4 levels had a significant prognostic value in NMIBC or MIBC. Urine levels correlated with tumor expression and serum levels in the Nectin-4 analysis, but not in the Nectin-2 analysis. Urine nectins are potential diagnostic biomarkers for BCa.

Funder

JSPS KAKENHI

Nara Medical University Grant-in-Aid for Collaborative Research Projects

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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