title: Klotho is silenced through promoter hypermethylation in gastric cancer.
abstract: As one of major epigenetic changes to inactivate tumor suppressor genes in human carcinogenesis, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes and predict the prognosis of cancer patients. In the present study, we found KL (klotho) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. KL expression was downregulated in primary gastric carcinoma tissues (n=22, p<0.05) and all of gastric cancer cells lines examined. Ectopic expression of KL inhibited the growth of gastric cancer cells partially through the induction of apoptosis, demonstrating a tumor suppressive role of KL in gastric cancer. Demethylation with 5-aza-2'-deoxycytidine (Aza) increased KL expression and KL promoter was hypermethylated in gastric cancer cell lines as well as some of primary gastric carcinoma tissues (47/99) but none of normal gastric tissues. Importantly, promoter methylation of KL was significantly associated with the poor outcome of gastric cancer patients (p=0.025, Log-rank test), highlighting the relevance of epigenetic inactivation of KL in gastric carcinogenesis. As a summary, we found that KL is a novel tumor suppressor gene epigenetically inactivated in gastric cancer and promoter methylation of KL could be used to predict the prognosis of gastric cancer patients.
authors.forename: Liangjing
authors.initials: L
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Jie
authors.forename: Haiqi
authors.initials: H
authors.lastname: Lu
authors.forename: Shengjie
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lin
authors.forename: Emily Ky
authors.initials: EK
authors.lastname: Lam
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin