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.

Laminin γ2‐enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via integrin α3‐dependent uptake by lymphatic endothelial cells

“…Kamada et al . identified urinary laminin γ2 as a novel biomarker of nonmuscle invasive urothelial carcinoma; however, it was not determined whether laminin γ2 was present in urinary EVs …”

Ln‐γ 2 chain of laminin‐332 is a useful marker in differentiating between benign and malignant sclerosing adnexal neoplasms

“…The monomeric form of Ln‐γ 2 has been detected in various carcinomas (pancreas, stomach, tongue, oesophagus, colorectal, lung and cervix) . Recently, Ln‐γ 2 has been reported as a useful novel biomarker for some carcinomas (urothelial carcinoma, hepatocellular carcinoma) . Studies show that Ln‐γ 2 is overexpressed at the invasive front of a variety of carcinoma tissue as well as in highly invasive cancer cells, and that such cells secrete a large amount of cleaved forms of Ln‐γ 2 in conditioned medium .…”

Serum monomeric laminin‐γ2 as a novel biomarker for hepatocellular carcinoma

“…(13)(14)(15)(16)(17)(18)(19) Our preliminary results indicated that elevated serum monomeric Ln-c2 levels could be observed in patients with various malignancies, such as pancreatic adenocarcinoma (data not shown) and bladder carcinoma. (21) Although further analysis is required, serum monomeric Ln-c2 is a potentially useful biomarker for the screening of cancer in various organs, similar to the carcinoembryonic antigen.…”

“…Therefore, the presence of monomeric Ln‐γ2 in the serum may be useful as a biomarker for HCC. In an earlier study, we developed a monoclonal antibody that preferentially recognizes the monomeric form of Ln‐γ2 and used it for ELISA to detect the Ln‐γ2 chain . We also developed a fully automated highly sensitive detection method for serum monomeric Ln‐γ2 based on a chemiluminescent immunoassay (CLIA).…”

“…In an earlier study, we developed a monoclonal antibody that preferentially recognizes the monomeric form of Ln-c2 (20) and used it for ELISA to detect the Ln-c2 chain. (21) We also developed a fully automated highly sensitive detection method for serum monomeric Ln-c2 based on a chemiluminescent immunoassay (CLIA). With this method, a linear calibration curve was obtained in the range of 10 000-20 000 pg/mL and serum monomeric Ln-c2 could be stably measured within 20 min (Nakagawa M, manuscript in preparation).…”