Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

Yamamoto,Yoshiaki; Suehiro,Yutaka; Suzuki,Atomu; Nawata,Ryosuke; Kawai,Yoshihisa; Inoue,Ryo; Hirata,Hiroshi; Matsumoto,Hiroaki; Yamasaki,Takahiro; Sasaki,Kohsuke; Matsuyama,Hideyasu

doi:10.3892/ol.2017.6233

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

Authors:
- Yoshiaki Yamamoto
- Yutaka Suehiro
- Atomu Suzuki
- Ryosuke Nawata
- Yoshihisa Kawai
- Ryo Inoue
- Hiroshi Hirata
- Hiroaki Matsumoto
- Takahiro Yamasaki
- Kohsuke Sasaki
- Hideyasu Matsuyama
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Affiliations: Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan, Department of Oncology and Laboratory Medicine, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan, Department of Pathology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi 755‑8505, Japan
Published online on: May 24, 2017 https://doi.org/10.3892/ol.2017.6233
Pages: 1193-1199

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Abstract

Accumulating evidence has suggested that germline DNA copy number variations (CNVs) affect various disorders, including human malignancies. However, the significance of CNVs in non‑muscle invasive bladder cancer (NMIBC) remains unclear. The purpose of the present study was to identify the role of CNVs in NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to search for candidate CNVs associated with NMIBC susceptibility. Quantitative polymerase chain reaction was carried out to evaluate CNVs associated with patient outcome in 189 NMIBC cases. In total, 11 CNVs were associated with NMIBC risk in array CGH analysis. Out of the 189 CNVs examined, family with sequence similarity 81 member A (FAM81A) and proprotein convertase subtilisin/kexin type 6 (PCSK6) CNVs exhibited a significant association with recurrence and disease progression in NMIBC. PCSK6 has been reported to regulate proliferation and tumor progression in breast and prostate malignancies. Notably, patients with pT1 stage had significantly lower PCSK6 relative copy number than those with pTa (P=0.0196). In multivariate analyses, PCSK6 copy number was an independent prognostic factor for progression‑free survival (P=0.0456; risk ratio, 2.17; 95% confidence interval, 1.02‑4.82). These data suggest that PCSK6 CNV is a potential new tumor marker for estimating disease progression in NMIBC.

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