title: Detection of aberrant hypermethylated spastic paraplegia-20 as a potential biomarker and prognostic factor in gastric cancer.
abstract: The aim of this study was to evaluate hypermethylation of the spastic paraplegia-20 promoter as a potential biomarker and prognostic factor in gastric cancer. Four human gastric cancer cell lines, 41 primary gastric cancer tissue samples and corresponding peripheral blood samples, and blood samples of 21 healthy individuals were analyzed using methylation-specific polymerase chain reaction. Additionally, the expression of Spartin, the protein product encoded by spastic paraplegia-20, was analyzed in tissues from 119 gastric cancer patients who underwent radical gastrectomy at Xi'an Jiaotong University between 2005 and 2010. Hypermethylation of the spastic paraplegia-20 promoter was observed in 26 of 41 (63.4 %) primary tumors and 1 of 35 (2.9 %) adjacent normal gastric tissues (P < 0.001). Among matched peripheral blood samples from gastric cancer patients, 48.8 % exhibited hypermethylation of the spastic paraplegia-20 promoter. In contrast, no methylation of the spastic paraplegia-20 promoter was observed in blood samples from 21 healthy individuals (P < 0.001). Additionally, demethylation by 5-aza-dC treatment led to gene reactivation in gastric cancer cells exhibiting hypermethylation of the spastic paraplegia-20 promoter. Finally, immunohistochemical staining indicated that low expression of Spartin was a prognostic factor predicting poor outcomes in gastric cancer patients (P = 0.037). These findings suggested that hypermethylation of the spastic paraplegia-20 promoter occurred frequently in gastric cancer and could represent a novel prognostic factor. Furthermore, detection of this molecular feature in the peripheral blood of gastric cancer patients suggested that evaluation of the methylation state of the spastic paraplegia-20 promoter may be used as a noninvasive screening method.
authors.affiliation: Oncology Department, The First Affiliated Hospital, Xi'an Jiaotong University, 277 W. Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Song
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.forename: Dongmei
authors.initials: D
authors.lastname: Diao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xuandi
authors.initials: X
authors.lastname: Wu
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Chengxue
authors.initials: C
authors.lastname: Dang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D011506:Proteins; C464787:SPART protein, human; D001374:Azacitidine