title: Enhanced serum methylated p16 DNAs is associated with the progression of gastric cancer.
abstract: OBJECTIVE
  The present study is to evaluate the effect of methylated p16 on the progression in patients with gastric cancer (GC), and develop a useful biomarker for predicting patient's prognosis.
  
  
  METHODS
  Methylation status of p16 in GC, their corresponding para-cancerous histological normal tissues (PCHNTs), preoperative peritoneal washes (PPWs) and serum were assessed using real-time methylation specific-PCR (MSP).
  
  
  RESULTS
  The frequency of p16 methylation was significantly higher in GC tissues (85.9%; 79/92) than that in paired PCHNTs (12.0%; 11/92) (P<0.0001). p16 methylation correlated closely with lymph node metastasis, peritoneal metastasis, TNM stage, et al (all P<0.05). Both frequency of p16 methylation in PPWs and serum were 79.7% (63/92). The Aζ value of the receiver-operator characteristic curve for methylated p16 was 0.899 for serum and PPWs, compared to that in GC tissues. The patients with elevated methylated p16 levels in tumor tissues had poorer disease-free survival (DFS) rates than those without (P=0.042). There is a narrow significant difference in median survival time of more than 30 months between patients with and without preoperatively detectable methylated p16 in serum (P=0.057). Methylated p16 in PPWs revealed no significant association with survival (P=0.129). Cox regression analysis showed that serum methylated p16 DNAs was an independent risk factor for GC patients, with a remarkable decrease in DFS 30 months after surgical resection of the gastric tumor.
  
  
  CONCLUSIONS
  Serum methylated p16 DNAs might serve as a potential biomarker for the progression and a prognostic factor in gastric cancer patients.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lv
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Jiang-Liu
authors.initials: JL
authors.lastname: Yu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Lian-Lian
authors.initials: LL
authors.lastname: Hong
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China ; The Central Laboratory, Zhoushan Hospital Zhoushan 316000, P. R. China.
authors.forename: Wang-Yu
authors.initials: WY
authors.lastname: Zhu
authors.affiliation: Department of Surgical Oncology, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Yu
authors.affiliation: Department of Surgical Oncology, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Xin-Bao
authors.initials: XB
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University Zhengzhou 450052, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center No. 38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P. R. China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010534:Peritoneal Neoplasms / Q000175:diagnosis; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D004247:DNA
keywords: Gastric carcinoma; methylation; p16 gene; peritoneal micrometastasis; prognosis