title: Urinary laminin-γ2 is a novel biomarker of non-muscle invasive urothelial carcinoma.
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.
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kamada
authors.affiliation: Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Koshikawa
authors.affiliation: Division of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minegishi
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawada
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Karashima
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.affiliation: Institute of Medical Science, University of Tokyo, Tokyo, Japan.|Kanazawa University, School of Medicine, Kanazawa, Japan.
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000652:urine*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C400567:LAMC2 protein, human; D007797:Laminin
keywords: Biomarker; diagnosis; laminin-γ2; urine; urothelial cancer (UC)