Role of Klotho protein in tumorigenesis, cancer progression, and prognosis in patients with high-grade glioma

Abstract Klotho, a single-pass transmembrane protein associated with premature aging, acts as a tumor suppressor gene by inhibiting insulin/insulin-like growth factor-1 and fibroblast growth factor pathways. Downregulated Klotho expression is reported in melanoma, mesothelioma, bladder, breast, gastric, cervix, lung, and kidney cancers, and is associated with a poor prognosis. Klotho expression and Klotho promoter hypermethylation are predictive factors for patient prognosis. To investigate the potential role of Klotho in glioblastoma-multiforme (GBM), 22 GBM samples were collected from the Sheba Tumor Bank and examined. We found that increased Klotho mRNA expression predicted longer survival (p=0.03) of GBM patients. Methylation analysis was performed on bisulfite-treated DNA from the GBM patient samples using ionization time-of-flight mass spectrometry according to the Sequenom EpiTYPER protocols. Klotho promoter hypermethylation was detected in 65% of the GBM samples, and correlated significantly with improved survival (p