title: Clinical significance of α‑ and β‑Klotho in urothelial carcinoma of the bladder.
abstract: Non-muscle invasive bladder cancer (NMIBC) accounts for ~70% of all bladder cancers. One of the serious clinical issues related to the management of NMIBC is that it has significant potential to progress to muscle invasive bladder cancer (MIBC) after initial treatments. α‑Klotho (KLα), originally identified as an anti‑aging gene, has recently been reported to have antitumor effects in various malignancies. In contrast, β‑Klotho (KLβ) has been reported to have protumoral functions. However, the associations between KLα/KLβ and the biological behavior of urothelial carcinoma remain unclear. In the present study, we evaluated the association between clinicopathological background factors of NMIBC and the expression levels of KLα or KLβ. A high expression level of KLβ, but not KLα, was an independent predictive factor of short progression‑free survival for NMIBC. An elevated level of KLβ correlated with a higher incidence of lymphovascular invasion (LVI). We added in vitro assays using human bladder cancer cell lines to investigate the role of KLβ. Treatment with exogenous KLβ protein increased the proliferation, migration, transendothelial migration abilities and anchorage‑independent growth of the cell lines. In addition, the KLβ concentration in voided urine samples obtained before initial transurethral surgery was quantitated with enzyme‑linked immunosorbent assay (ELISA). The urine KLβ concentration was found to be higher in patients with bladder cancer than that in healthy volunteers. Our results suggest that KLβ plays important roles in tumor invasion and progression, and its concentration may be a valuable urine‑based marker for the detection of bladder cancer.
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Shunta
authors: S
authors: Hori
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Makito
authors: M
authors: Miyake
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Sayuri
authors: S
authors: Onishi
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Yoshihiro
authors: Y
authors: Tatsumi
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Yosuke
authors: Y
authors: Morizawa
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Yasushi
authors: Y
authors: Nakai
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Satoshi
authors: S
authors: Anai
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Nobumichi
authors: N
authors: Tanaka
authors: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.
authors: Kiyohide
authors: K
authors: Fujimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D000090265:Klotho Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C538995:KLB protein, human; D008565:Membrane Proteins; D005966:Glucuronidase; D000090265:Klotho Proteins