Urinary laminin‐γ2 is a novel biomarker of non‐muscle invasive urothelial carcinoma

Cancer Science

Masayuki Kamada²  Naohiko Koshikawa¹  Tomoko Minegishi¹  Chiaki Kawada²  Takashi Karashima²  Taro Shuin² 

[1] Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama, Japan;Department of Urology, Kochi Medical School, Kochi, Japan

关键词: Biomarker;    diagnosis;    laminin‐γ2;    urine;    urothelial cancer (UC);   

DOI  :  10.1111/cas.12832

来源: Wiley

【 摘 要 】

Abstract

Lack of appropriate biomarkers has hampered early detection of urothelial cancer (UC), therefore, development of biomarkers for its diagnosis at earlier stages is of importance. Laminin-332 (Ln-332, formerly Ln-5), a component of basement membranes, consists of Ln-α3, Ln-β3, and Ln-γ2 polypeptides. However, monomeric Ln-γ2 alone is frequently expressed in malignant neoplasms. If Ln-γ2 is also expressed in UC and secreted into the urine, its detection could be useful for UC diagnosis. Here, we evaluated Ln-γ2 levels from 60 patients with urinary diseases (including UC) by Western blotting, and detected it in approximately 53% of UC cases. Using immunohistochemistry, we confirmed Ln-γ2 expression in UC tissues that were positive for Ln-γ2, whereas Ln-α3 expression was absent. We next developed a sandwich enzyme-linked immunosorbent assay and applied it for screening 39 patients with non-muscle invasive UC and 61 patients with benign urologic diseases. The Ln-γ2 levels were higher in UC patients than in those with benign urologic diseases. Ln-γ2 was detected even in patients with earlier stages of UC, such as Ta, T1, or carcinoma in situ. The sensitivity of Ln-γ2 testing for UC was 97.4%, and the specificity was 45.9%, using a cut-off of 0.5 μg/g∙crn. Ln-γ2 had greater diagnostic value for detecting non-muscle invasive UC compared to conventional urine cytology and available biomarkers for UC, and may be useful as a urine biomarker for the diagnosis and monitoring of UC.

【 授权许可】

CC BY-NC   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.