title: Clinical significance of the methylated cytosine-phosphate-guanine sites of protocadherin-10 promoter for evaluating the prognosis of gastric cancer.
abstract: BACKGROUND
  Protocadherin-10 (PCDH10) has been identified as a tumor suppressor gene in multiple carcinomas. In this study, we intended to elucidate the clinical applicability of the methylation of CpG sites of PCDH10 promoter for prognostic prediction in gastric cancer (GC).
  
  
  METHODS
  Qualitative and quantitative detections of PCDH10 promoter methylation were performed with methylation-specific polymerase chain reaction (MSP) and bisulphite genomic sequencing, respectively. The methylated statuses of 27 cytosine-phosphate-guanine (CpG) sites in PCDH10 promoter were detected in a series of 458 GC tissues to supply precise information of prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed.
  
  
  RESULTS
  Protocadherin-10 promoter methylation was found in 91.92% in all patients. Gastric cancer patients with 5 or more methylated CpG sites of PCDH10 promoter was significantly associated with poorer survival (p = 0.038). Meanwhile, methylation of combined CpG (-115, -108, -13, and +3) sites was also identified to provide elaborate survival discrimination for GC patients (p = 0.044). On multivariate survival analysis, methylation of combined CpG (-115, -108, -13, and +3) sites (hazard ratio [HR] = 1.255; p = 0.049) was identified to be an independent prognostic indicator of GC, as were N stage and T stage. Additionally, the methylation of combined CpG (-115, -108, -13, and +3) sites had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other 2 independent predictors of the survival. Ultimately, we demonstrated that the methylation of combined CpG (-115, -108, -13, and +3) sites was negatively associated with PCDH10 expression in GC tissues.
  
  
  CONCLUSIONS
  The methylated CpG sites of PCDH10 promoter had significant applicability for clinical evaluation of the prognosis of GC.
authors.affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: Central Laboratory, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Ying
authors.affiliation: Central Laboratory, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Digestive Disease, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China. Electronic address: tjhaoxishan@sohu.com.
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C438603:PCDH10 protein, human; D000091363:Protocadherins